Development of mousemodels representing human spontaneous ovarian cancer has been hampered by the lack of understanding of the etiology of this very complex disease. Mousemodels representing the different...Full Text Available
The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa...Full Text Available
Recently, there has been significant progress in the development of genetically-engineered mouse (GEM) models. By introducing genetic alterations and/or signaling alterations of human pancreatic cancer...Full Text Available
Transgenic mousemodels have contributed considerably to our understanding of the cellular and molecular mechanisms by which androgens control spermatogenesis. Cell-selective ablation of the androgen...Full Text Available
Persistent hepatitis C virus (HCV) infection affects 170 million people worldwide. Acute HCV infection is often asymptomatic, but many infected individuals develop persistent infections that may lead to development of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. Thus, an HCV vaccine that could significantly lower the chronicity rate would have a major impact on the disease burden. Unfortunately, HCV is a highly mutable virus, and escape mutations can undermine vaccine-induced virus-specific immunity. Also, HCV exists as multiple genotypes, and so genotype-specific vaccines might be required to achieve broad protection. Finally, vaccine development has been hampered by the lack of a small animal model and cell culture systems, but these are currently being established. Despite these obstacles, several vaccine candidates tested ...
The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain...Full Text Available
Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments....Full Text Available
Genetically identical rhesus monkeys would have tremendous utility as models for the study of human disease and would be particularly valuable for vaccine trials and tissue transplantation studies where...Full Text Available
Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential...Full Text Available
A rickettsia related to but distinct from the spotted fever agent, Rickettsia rickettsii, has been detected in 167 (18.9%) of 884 Rhipicephalus sanguineus taken off dogs in central and northern Mississippi. The organisms could readily be isolated in male meadow voles (Microtus pennsylvanicus), where it produced massive infections in the tissues of tunica vaginalis. It was practically nonpathogenic for male guinea pigs, although inoculation of these animals with infected tunica vaginalis of voles afforded in 30 of 38 instances solid immunity to challenge with virulent R. rickettsii. The Rhipicephalus rickettsia grew well in monolayers of chicken embryo fibroblast, Vero, mouse L, and HeLa cells. Cytopathogenic effects were minimal unless large concentrations of rickettsiae were used as inocula. It also could be established in embryonated hen eggs but only after injection of massive doses of L cell-propagated organisms. Serological tests (complement fixation, ...
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable...Full Text Available
Mousemodels have dramatically improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic...Full Text Available
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
... a flu shot There is a new nasal spray version of the vaccine, and it contains weakened ... the LAIV (Live Attenuated Influenza Vaccine). The nasal-spray flu vaccine contains three different live but weakened ...
home when you are sick helps everyone you care about Questions & Answers Flu Vaccine: Q&A Vaccine Dosage & Administration Vaccine Supply for 2011-12 Season Vaccine Supply and...
home when you are sick helps everyone you care about Questions & Answers Flu Vaccine: Q&A Vaccine Dosage & Administration Vaccine Supply for 2011-12 Season Vaccine Supply and...
home when you are sick helps everyone you care about Questions & Answers Flu Vaccine: Q&A Vaccine Dosage & Administration Vaccine Supply for 2011-12 Season Vaccine Supply and...
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
Significant emphasis has recently been placed on the characterization of the human cancer genome. This effort has been assisted by the development of new DNA sequencing technologies that allow...Full Text Available
Dominant mutations in sarcomere protein genes cause hypertrophic cardiomyopathy, an inherited human disorder with increased ventricular wall thickness, myocyte hypertrophy, and disarray. To understand...Full Text Available
AbstractStudies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been...Full Text Available
Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is...Full Text Available
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression...Full Text Available
BackgroundSeasonal influenza A infection affects a significant cohort of the global population annually, resulting in considerable morbidity and mortality. Therapeutic strategies...Full Text Available
Mousemodels 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
Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome type B) is a metabolic disorder with devastating clinical characteristics starting in early childhood and leading to premature death. A...Full Text Available
Background:Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of...Full Text Available
The formation of mammalian secondary palate requires a series of developmental events such as growth, elevation and fusion. Despite recent advances in the field of palate development, the process...Full Text Available
Purpose: Small animal micro-CT imaging is being used increasingly in preclinical biomedical research to provide phenotypic descriptions of genomic models. Most of this imaging is coincident...Full Text Available
BackgroundApolipoprotein E (ApoE), a cholesterol carrier associated with atherosclerosis, is a major risk factor for Alzheimer's disease (AD). The low-density lipoprotein receptor...Full Text Available
BackgroundDue to the high morbidity and mortality of fulminant hepatitis, early diagnosis followed by early effective treatment is the key for prognosis improvement. So far, little...Full Text Available
Inactivation of the RB tumor suppressor and activation of the MYC family of oncogenes are frequent events in a large spectrum of human cancers. Loss of RB function and MYC activation are thought to...Full Text Available
BackgroundNon-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize....Full Text Available
Spontaneous mousemodels 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
Changes in the number of chromosomes, but also variations in the copy number of chromosomal regions have been described in various pathological conditions, such as cancer and aneuploidy, but also in...Full Text Available
BackgroundStorage of RBCs is necessary for an adequate blood supply. However, reports have identified potential negative sequelae of transfusing stored RBCs. An animal...Full Text Available
SUMMARYAmeloblastin (AMBN) is the second most abundant extracellular matrix protein produced by the epithelial cells called ameloblasts and is found mainly in forming dental enamel....Full Text Available
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this p53-null ...
Ten children receiving maintenance dialysis were immunized with the standard dose of measles-mumps-rubella vaccine between 15 and 33 months of age. Immune responses to vaccination were determined using commercially available enzyme-linked immunosorbent assays for measles, mumps, and rubella viruses. Eight children responded to measles vaccine, 5 to mumps vaccine, 8 to rubella vaccine, and only 3 children to all three vaccines, compared with a seroconversion rate of over 90% to all three vaccines in healthy children (P less than 0.0001). We contend that the relatively poor immunocompetence of our dialysis patients explains their less than optimal vaccine response and suggest that children vaccinated while undergoing dialysis be tested to confirm serological evidence of immunity. PMID:1571219
Maintenance of genomic integrity in embryonic cells is pivotal to proper embryogenesis, organogenesis and to the continuity of species. Cultured mouse embryonic stem cells (mESCs), a model for early embryonic cells, differ from cultured somatic cells in their capacity to remodel chromatin, in their repertoire of DNA repair enzymes, and in the regulation of cell cycle checkpoints. Using 129XC3HF1 mESCs heterozygous for Aprt, we characterized loss of Aprt heterozygosity after exposure to ionizing radiation. We report here that the frequency of loss of heterozygosity mutants in mESCs can be induced several hundred-fold by exposure to 5-10Gy of X-rays. This induction is 50-100-fold higher than the induction reported for mouse adult or embryonic fibroblasts. The primary mechanism underlying the...
Abstract Crouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mousemodel 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 first candidate rotavirus vaccine was a live attenuated oral vaccine made by the classical empirical method of serial passage of virus in tissue culture cells. Current tetravalent vaccine candidates that are in the final stages of efficacy testing in the United States were made by genetic reassortment. This article briefly highlights how advances in the basic understanding of the molecular biology of rotaviruses have facilitated vaccine development. New approaches for second-generation vaccines and improvements in vaccine efficacy based on further exploitation of the tools and knowledge of rotavirus molecular biology and pathogenesis are discussed. PMID:8752289
A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mousemodel for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 figs., 1 tab.
Containing an epidemic at its origin is the most desirable mitigation. Epidemics have often originated in rural areas, with rural communities among the first affected. Disease dynamics in rural regions have received limited attention, and results of general studies cannot be directly applied since population densities and human mobility factors are very different in rural regions from those in cities. We create a network model of a rural community in Kansas, USA, by collecting data on the contact patterns and computing rates of contact among a sampled population. We model the impact of different mitigation strategies detecting closely connected groups of people and frequently visited locations. Within those groups and locations, we compare the effectiveness of random and targeted vaccinations using a Susceptible-Exposed-Infected-Recovered compartmental model on the contact network. Our simulations show ...
Ninety percent of foxes fed commercial ERA vaccine in a specially designed bait developed rabies serum neutralizing antibodies. The vaccine bait did not cause clinical signs of rabies when consumed...Full Text Available
BACKGROUND: Although the effectiveness of influenza vaccination in high-risk groups has been proven, vaccine coverage continues to be less than 50% in The Netherlands. To improve vaccination rates,...Full Text Available
SummaryBecause increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine-from virus-induced antibodies. Most of the currently...Full Text Available
The extensive diversity of Plasmodium falciparum antigens is a major obstacle to a broadly effective malaria vaccine but population genetics has rarely been used to guide vaccine design....Full Text Available
BackgroundThe first vaccine to prevent human papillomavirus (HPV) and cervical cancer has been licensed, and in future, vaccination may be routinely offered to 10–14 year...Full Text Available
The retinal degeneration 10 (rd10) mouse is a well-characterized model of autosomal recessive retinitis pigmentosa (RP), which carries a spontaneous mutation in the ? subunit of rod cGMP-phosphodiesterase (PDE?). Rd10 mouse exhibits photoreceptor dysfunction and rapid rod photoreceptor degeneration followed by cone degeneration and remodeling of the inner retina. Here, we evaluate whether gene replacement using the fast-acting tyrosine-capsid mutant AAV8 (Y733F) can provide long-term therapy in this model. AAV8 (Y733F)-smCBA-PDE? was subretinally delivered to postnatal day 14 (P14) rd10 mice in one eye only. Six months after injection, spectral domain optical coherence tomography (SD-OCT), electroretinogram (ERG), optomotor behavior tests, and immunohistochemistry showed tha...
Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the ...
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...
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 mousemodel 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...
We used a 13-year time series of abundance estimates of breeding Northern Saw-whet Owls (Aegolius acadicus), and of small mammals from central Ontario, Canada, to assess the numerical response of the owls to small-mammal prey species. We found that the finite rate of increase of breeding owls was directly related to estimates of red-backed vole (Myodes gapperi) abundance. Thus, it appeared that the owls were nomadic, and made decisions about where to breed based on vole supply. The owls showed a much weaker response to deer mouse (Peromyscus maniculatus) abundance. Across all years, 55% of variation in owl rate of increase could be uniquely attributed to vole abundance, whereas only 3% could be attributed to mouse abundance. Consistent with the model of nomadism, there was only a weak rela...
Background Identifying susceptibility genes for endophenotypes by studying analogous behaviors across species is an important strategy for understanding the pathophysiology underlying psychiatric disorders. This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior. Methods In the present study, novel automated registration methods for longitudinal behavioral assessment in home cages are used to screen a panel of recently generated mouse chromosome substitution strains that are very powerful in quantitative trait loci (QTL) detection of complex traits. In this way, we identified chromosomes regulating avoidance behavior (increased sheltering preference) independent of motor activity lev...
The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles...Full Text Available
Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)
The past three years of work for the Air Force Office of Scientific Research has resulted in the development of a congenic mousemodel of JP-8 jet fuel exposure, the role of substance P in the JP-8 jet fuel-induced lung injury process, and development of ...
Cordycepin has been shown to interfere with a myriad of molecular processes from RNA elongation to kinase activity, and prevents numerous inflammatory processes in animal models. Here we show in a mouse...Full Text Available
Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic ...
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.
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% ...
This issue has the following articles: (1) Deterrence with a Minimum Nuclear Stockpile - Commentary by Bruce T. Goodwin; (2) Enhancing Confidence in the Nation's Nuclear Stockpile - Livermore experts are participating in a national effort aimed at predicting how nuclear weapon materials and systems will likely change over time; (3) Narrowing Uncertainties - For climate modeling and many other fields, understanding uncertainty, or margin of error, is critical; (4) Insight into a Deadly Disease - Laboratory experiments reveal the pathogenesis of tularemia in host cells, bringing scientists closer to developing a vaccine for this debilitating disease. (5) Return to Rongelap - On the Rongelap Atoll, Livermore scientists are working to minimize radiological exposure for natives now living on or wishing to return to the islands.
Selected applications of novel techniques in Agricultural Biotechnology, Health Food formulations and Medical Biotechnology are being reviewed with the aim of unraveling future developments and policy changes that are likely to open new markets for Biotechnology and prevent the shrinking or closing of existing ones. Amongst the selected novel techniques with applications in both Agricultural and Medical Biotechnology are: immobilized bacterial cells and enzymes, microencapsulation and liposome production, genetic manipulation of microorganisms, development of novel vaccines from plants, epigenomics of mammalian cells and organisms, and biocomputational tools for molecular modeling related to disease and Bioinformatics. Both fundamental and applied aspects of the emerging new techniques are being discussed in relation to their anticipated, marked impact on future markets and present policy changes that are needed for success in either ...
There is significant interest in using computed tomography (CT) for in vivo imaging applications in mousemodels of disease. Most commercially available mouse x-ray CT scanners utilize a charge-coupled device (CCD) detector coupled via fibre optic taper to a phosphor screen. However, there has been little research to determine if this is the optimum detector for the specific task of in vivo mouse imaging. To investigate this issue, we have evaluated four detectors, including an amorphous selenium (a-Se) detector, an amorphous silicon (a-Si) detector with a gadolinium oxysulphide (GOS) screen, a CCD with a 3:1 fibre taper and a GOS screen, and a CCD with a 2:1 fibre taper and both GOS and thallium-doped caesium iodide (CsI:Tl) screens. The detectors were evaluated by measuring the modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), stability over multiple ...
There is a quest for the development of a new generation of vaccines consisting of well-defined subunit antigens. For a number of practical reasons it is attractive to develop vaccines on the basis...Full Text Available
The human immunodeficiency virus Tat protein is essential for virus replication and is a candidate vaccine antigen. Macaques immunized with Tat or chemically modified Tat toxoid having the same clade...Full Text Available
The development of an HIV vaccine will require a more precise understanding of the immunological and virological underpinnings of HIV infection. Magnetofection, the process of magnetizing HIV...Full Text Available
Although major inroads into making antiretroviral therapy available in resource-poor countries have been made, there is an urgent need for an effective vaccine administered shortly after birth, which...Full Text Available
... Weiss, S., D. Kobiler, H. Levy, H. Marcus, A. Pass, N. Rothschild, and Z ... of Bacillus anthracis spores conferred by a protective antigen-based vaccine in rabbits ...
The attitude of Nigerian mothers, mainly Yoruba, towards measles vaccine and other aspects of prevention are influenced by different perceptions of the cause of measles. There is a significant correlation...Full Text Available
The entire genome of rabies virus vaccine strain Flury-LEP-C, a Chinese variant of the rabies virus vaccine strain Flury-LEP, was sequenced. The overall length of the genome of Flury-LEP-C strain was...Full Text Available
BackgroundAlthough the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held...Full Text Available
During the anamnestic response, the sera of four rabbits immunized with a polyvalent pneumococcal vaccine contained large amounts of cryoglobulins belonging to the G and M immunoglobulin classes. These...Full Text Available
Splenectomy or pretreatment of adult hamsters with cyclophosphamide (Cytoxan) increased the lethality of the TC-83 vaccine strain of Venezuelan encephalitis virus (VEE), inoculated subcutaneously, from 12% for normal hamsters to 75 and 76% respectively. A...
PurposeWe previously reported a randomized phase II clinical trial combining a poxvirus-based vaccine encoding PSA with radiotherapy in patients with localized prostate...Full Text Available
Lethal yellow (A{sup y}) is a mutation at the mouse agouti locus in chromosome 2 that causes a number of dominant pleiotropic effects, including a completely yellow coat color, obesity, an insulin-resistant type II diabetic condition, and an increased propensity to develop a variety of spontaneous and induced tumors. Additionally, homozygosity for A{sup y} results in preimplantation lethality, which terminates development by the blastocyst stage. The A{sup y} mutation is the result of a 170-kb deletion that removes all but the promoter and noncoding first exon of another gene called Raly, which lies in the same transcriptional orientation as agouti and maps 280 kb proximal to the 3{prime} end of the agouti gene. The authors present a model for the structure of the A{sub y} allele that can explain the dominant pleiotropic effects associated with this mutation, as well as the recessive lethality, which is unrelated to the agouti gene.
The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study,...Full Text Available
We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone...Full Text Available
A field study was conducted under commercial feedlot conditions at 2 sites in western Canada to determine the relative effects of a univalent viral vaccine (MLV 1) program versus a multivalent viral...Full Text Available
AbstractThe elucidation of the human and mouse genome sequence and developments in high-throughput genome analysis, and in computational tools, have made it possible to profile entire...Full Text Available
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 mousemodel. 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...
Introduction: Tumor-derived heat shock protein (HSP)-peptide complexes (HSPPCs) induced immunity against malignancies in preclinical trials, working across tumor types and bypassing the need to identify single immunogenic peptides. These results paved the way for the use of human gp96 obtained from autologous tumor samples as an anti-cancer vaccine. Areas covered: Autologous tumor-derived HSP gp96 peptide complex (HSPPC-96) vaccine is emerging as a tumor- and patient-specific cancer vaccine, with confirmed activity in several malignancies. It has been tested in Phase III clinical trials in advanced melanoma and kidney cancer with evidence for efficacy in patients with earlier stage disease. HSPPC-96-based vaccine demonstrated an excellent safety profile, thus emerging as a novel therapeuti...
In this paper, we propose and implement a website of post-processing system for finite element analysis (WebDFEA). Finite element analysis is a computer-aided engineering tool and is popular for static/dynamic structure analysis. It includes three processing systems where post-processing system is to graphically demonstrate the analysis result of a structure model analyzed by finite element method. WebDFEA performs as a website. It is cross-platform because it can auto-detect a client computer platform and auto-download proper OpenGL API for drawing computer graphics. It can draw precise graphics on webpage which can be free controlled by the mouse as a manner in professional software. A database server is involved to store finite element model data and its analysis result. The graphic use...
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...
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 mousemodel. Topical CEES treatment at high doses caused a significant dose-dependent increase in skin bi-fold thickness indicating edema. Histopathological e...
The process of mouse skin tumor formation is subdivided into three operational stages. These stages include initiation, promotion and progression. Ionizing radiation has been found to be a weak initiating agent in the production of malignant squamous cell carcinomas, a complete carcinogen and an agent effective in causing tumor progression. Four skin tumor histologies have been seen with ionizing radiation: benign papillomas, squamous (SCC) and basal (BCC) cell carcinomas and fibrosarcomas. Distinct non-ras transforming genes have been detected in radiation initiated SCCs. A benign papilloma cell line (308) was used as a model system to study ionizing radiation induced progression. A variant 308 cell line (308 10 Gy 5) derived by irradiation of the parental 308 cell has been characterized. The 308 10 Gy 5 cells unlike the parental 308 cells from malignant tumors in athymic nude mice upon subcutaneous injection. The variant 308 10 Gy 5 cells ...
IntroductionThe outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal...Full Text Available
Age-related alterations in the cellular composition of the B lineage are a major cause of the poor antibody response to vaccination and to infectious agents among the elderly population. The mechanisms...Full Text Available
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A letter of inquiry was sent to 21 countries in Europe to ascertain their experience of diphtheria during the last 20 years. An analysis of the 15 replies showed that all relied on childhood vaccination...Full Text Available
BackgroundAlthough advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues...Full Text Available
... view on the utility of such attacks, see JH Rothschild, Tomorrow's Weapons ... Aum Shinrikyo may have had a stolen vaccine anthrax strain incapable ...
Background and aims. The multiplicity of vaccine injections during childhood leads to iterative painful and stressful experiences which may lead in turn to anticipated pain and then possibly to a true needle phobia. We aimed at evaluating a multifactorial strategy of pain management combining pharmacological and non-pharmacological approaches during vaccination, as compared to usual care, in 4- to 12-year-old children. Methods. In all, 239 children were enroled by 25 family practitioners in an open-label study. After a pseudo-randomization, usual pain management (n = 132) was compared to a multifactorial strategy (n = 107) associating preliminary application of an anesthesic patch, preferential use of specified vaccines, child education by the parents and the doctor, parental accompaniment...
BackgroundMycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including...Full Text Available
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...
The ultimate goal of this research is to generate and apply novel technologies to speed completion and integration of the human genome map and sequence with biomedical problems. To do this, techniques were developed and genome-wide resources generated. This includes a genome-wide Mapped and Integrated BAC/PAC Resource that has been used for gene finding, map completion and anchoring, breakpoint definition and sequencing. In the last period of the grant, the Human Mapped BAC/PAC Resource was also applied to determine regions of human variation and to develop a novel paradigm of primate evolution through to humans. Further, in order to more rapidly evaluate animal models of human disease, a BAC Map of the mouse was generated in collaboration with the MTI Genome Center, Dr. Bruce Birren.
Purpose. The paper introduces a novel design of air-core inductive sensors in printed circuit board (PCB) technology for a tongue control system. The tongue control system provides a quadriplegic person with a keyboard and a joystick type of mouse for interaction with a computer or for control of an assistive device. Method. Activation of inductive sensors was performed with a cylindrical, soft ferromagnetic material (activation unit). Comparative analysis of inductive sensors in PCB technology with existing hand-made inductive sensors was performed with respect to inductance, resistance, and sensitivity to activation when the activation unit was placed in the center of the sensor. Optimisation of the activation unit was performed in a finite element model. Results. PCBs with air-core indu...
BackgroundThe Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against...Full Text Available
Vibrio cholerae 638 (El Tor, Ogawa), a new CTXΦ-negative hemagglutinin/protease-defective strain that is a cholera vaccine candidate, was examined for safety and immunogenicity...Full Text Available
Adenovirus vaccine vectors derived from rare human serotypes have been shown to be less potent than serotype 5 (Ad5) at inducing immune responses to encoded antigens. To identify highly immunogenic...Full Text Available
...INFORMATION Diarrhoeal disease Food safety and foodborne illness Enterohaemorrhagic Escherichia coli (EHEC) Cholera WHO PROGRAMMES AND ACTIVITIES Child and Adolescent Health and Development (...FOS) Initiative for Vaccine Research (IVR) TECHNICAL INFORMATION Vaccine research: diarrhoeal diseases Cholera Water-related diseases Household water treatment and safe storage WHO Global Salm-Surv ...PUBLICATIONS Diarrhoea: child and adolescent health Diarrhoea: cholera RELATED TOPICS - Child health - Water - Food safety - Cholera - Travel - Breastfeeding ...
The use of tick vaccines in mammalian hosts has been shown to be the most promising alternative tick control method to current use of acaricides, which suffers from a number of limitations. However,...Full Text Available
The efficacy of a heat inactivated hepatitis B virus vaccine, containing 3 micrograms hepatitis B surface antigen (HBsAg), was studied in a high risk group of 800 susceptible homosexual men by a randomised...Full Text Available
Veterinarians and farmers employing multivalent killed vaccines in lactating dairy cows have reported transient losses in milk production. Few studies have quantified this loss. In this report, effects...Full Text Available
The Yellow Fever Vaccine 17D (YFV17D) has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) resulting in construction of YFV17D/LASV-GPC recombinant virus. The virus...Full Text Available
BackgroundThe malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant...Full Text Available
Mouse genetic resources include inbred strains, recombinant inbred lines, chromosome substitution strains, heterogeneous stocks, and the Collaborative Cross (CC). These resources were generated through...Full Text Available
BackgroundThe dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin...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 first cell lineage specification in mouse embryo development is the formation of trophectoderm (TE) and inner cell mass (ICM) of the blastocyst. This article is to review and discuss the...Full Text Available
Normal mouse epidermis constitutively expresses prostaglandin-H synthase 1 (PGHS-1) but no PGHS-2. Acute inflammation and epidermal hyperplasia, (hyperplastic transformation), as evoked in adult mouse...Full Text Available
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available
Recombinant mouse UDP-glucose pyrophosphatase (UGPPase), encoded by the Nudt14 gene, was produced in Escherichia coli and purified close to homogeneity. The...Full Text Available
Reaggregated cells from 6- to 8-day-old mouse cerebella have been used to raise antibodies in rabbits. The interaction of these antibodies with cerebellar cell surface components was assessed by cytotoxicity...Full Text Available
In preimplantation mouse development, the first cell lineages to be established are the trophectoderm (TE) and inner cell mass. TE possesses epithelial features, including apical-basal cell polarity...Full Text Available
This report presents the methodology and the results from the modelling of an open repository for spent nuclear fuel in Laxemar. Specifically, the present work analyses the hydrological effects of the planned repository during the construction and operational phases when it is open, i.e. air-filled, and hence may cause a disturbance of the hydrological conditions in the surroundings. The numerical modelling is based on the SDM-Site Laxemar MIKE SHE model. The modelling was divided into three steps. The first step was to update the SDM-Site Laxemar model with a new hydrogeological bedrock model. The other main updates were an increase of the depth of the MIKE SHE model domain, enhanced vertical computational resolution and that the drainage of the Aespoe Hard Rock Laboratory was included in the model. The resulting ...
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mousemodel. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of proliferating cell ...
Despite extensive clinical use of thallium-201 (/sup 201/Tl) for myocardial imaging, the effect of ischemia on myocardial accumulation and release of /sup 201/Tl independent of flow has not been fully defined. Therefore, myocardial accumulation of /sup 201/Tl in response to ischemic-like myocardial injury was assessed in vitro using the cultured fetal mouse heart preparation. Cultured fetal mouse hearts (n . 311) were subjected to injury simulating ischemia by deprivation of oxygen and oxidizable substrates for periods ranging from 15 minutes to 10 hours. The extent of irreversible injury was determined by the percentage of lactic dehydrogenase (LDH) lost from the hearts to the culture medium during recovery from injury. Injury was essentially reversible at 1 hour of insult. The fraction of /sup 201/Tl content in injured compared with control hearts was not significantly lower after 1 hour of insult. By 3 hours of insult, irreversible injury as ...
The issue of the duration of immunity, particularly for the modified live viral components of veterinary vaccines, has been a significant part of the recent vaccination debate. One manufacturer has increased the recommended booster interval for these components to 3 years give name and another now states `up to 4 years' immunity.There remain many unanswered questions regarding this duration of immunity (DOI). Studies suitable for data sheet claims are time consuming and costly and can only be performed in laboratory dogs under tightly controlled conditions. Evidence from rabies serology testing in the UK shows that the response of individual animals to routine vaccination is highly variable. Much of the published field evidence on the persistence of antibody titres originates from North Am...
In this paper we present an overview of the literature on efficacy and safety trials of the various pneumococcal conjugate vaccines on the market (PCV7) and in development (PCV9, PCV11 and allegedly PCV10 and PCV13), as well as of observations from post-licensure studies. Seven- (PCV7) and nine-valent PCV (PCV9) are reported to be sufficiently immunogenic after administration of a 3+1 schedule in infants in various RCTs. PncOMPC (PCV7 with a protein of N. meningitidis as a carrier) is less immunogenic, though this may have no repercussions for the protective efficacy against clinical disease. PCV7 is 82-97% efficacious against vaccine serotype (VT) IPD, 90% efficacious against (clinically diagnosed) pneumococcal pneumonia, and, like the 11-valent PCV, 57% efficacious against VT acute otiti...
Oral vaccination is the most desirable immunization method by which to prevent fish disease occurring at the early larval stage. We developed an Escherichia coli-based oral nervous necrosis virus (NNV) subunit vaccine and demonstrated its effectiveness in orange spotted grouper (Epinephelus coioides) fry. However, the incubation period was determined to be over 2weeks. To enhance the efficacy and shorten the incubation period, a safe and digestible biological adjuvant should be found. Vibrio anguillarum, a common marine bacterium with immune-stimulatory capability was selected as an expression host. An expression vector containing its heat shock protein 60 gene (groE) as an inducible promoter was constructed to express recombinant NNV coat protein as an antigen. The recombinant V. anguilla...
Recommended treatment of chronic hepatitis B with interferon-α and/or nucleos(t)ide analogues does not lead to a satisfactory result. Induction of HBV-specific T cells by therapeutic...Full Text Available
The trematode Fasciola hepatica (Fa.he.) is a common parasite of human and livestock. The hemoglobin (Hb) of Fa.he., a potential immunogen, was chosen for characterization...Full Text Available
BackgroundTrypanosoma cruzi, the etiologic agent of Chagas Disease, is a major vector borne health problem in Latin America and an emerging...Full Text Available
AbstractIndividual informed consent is a key ethical obligation for clinical studies, but empirical studies show that key requirements are often not met. Common recommendations to strengthen...Full Text Available
In the absence of a vaccine, there is an urgent need for the development of safe and effective topical microbicides to prevent the sexual transmission of human immunodeficiency virus type 1 (HIV-1)....Full Text Available
BackgroundPolychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose–response relationship and possible vulnerable time windows of exposure are...Full Text Available
A preventive medicine program of rubella control for trainees at the Air Force Military Training Center, Lackland AFB, Texas, was begun in October 1977. Incoming trainees were screened for rubella susceptibility,...Full Text Available
...broad range of experience in designing and building research and development laboratories for products such as vaccines, blood and sera, biological products, medical devices, solid dosage forms , highly potent products and cytotoxic material. We also have experience in a range of modular laboratories for TSE research, ...
A prospective cohort study was undertaken in two commercial California dairies. The treatment group, 246 cows, received three doses of a whole cell bacterin of J5 Escherichia coli (mutant of E. coli...Full Text Available
BackgroundSurrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified.MethodsHIV-infected...Full Text Available
Israel has faced the challenge presented by epidemic poliomyelitis by using different immunization strategies. In the 1950s, inactivated poliovirus vaccine (IPV) helped to reduce the total burden of...Full Text Available
In vivo plasminogen responses to various stimuli were studied. Plasminogen-125I was prepared and used first for metabolic studies of plasminogen in control dogs. The average results were:...Full Text Available
Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective. PMID:7561195
Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat...Full Text Available
Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens...Full Text Available
... were erroneous. The oriental rat flea, Xenopsylla cheopis Rothschild, is considered to be the primary vector of ... laboratory and production of Weigl's exanthematous typhus vaccine. In Maintenance of hum...
In this report we define the parameters of the human immune response after immunization with hepatitis B vaccine. 2 wk after booster immunization, there is significant spontaneous secretion of antibody...Full Text Available
The use of dendritic cells (DCs) as a cellular adjuvant is a promising approach to the immunotherapy of cancer. It has previously been demonstrated that DCs pulsed ex vivo with Toxoplasma gondii...Full Text Available
Approximately 30% of foxes given two doses of an inactivated rabies antigen delivered directly into the intestinal tract developed an immune response as measured by rabies serum neutralizing antibodies....Full Text Available
Increasing numbers of human cowpox virus infections that are being observed and that particularly affect young non-vaccinated persons have renewed interest in this zoonotic disease. Usually causing...Full Text Available
BackgroundThe objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the...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
Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue...Full Text Available
The identification of the protein targets for dengue virus-specific T lymphocytes may be useful for planning the development of subunit vaccines against dengue. We studied the recognition by murine...Full Text Available
vaccination card during trial enrollment at the KEMRI/CDC site in Kenya. (Alan Rubin, KEMRI) KEMRI Clinical Officer Paul Ogai reviews a prospective participant's...
Public health activities, especially infectious disease control, depend on effective teamwork. We present the results of a pilot audit questionnaire aimed at assessing the quality of public health services...Full Text Available
... A better understanding of the links between nutrients, the gut microbiome and the intestinal immune system is likely to pave the way to the development of innovative approaches that target activation of specific immunological pathways for promoting the hostrsquo;s gut defense. Such knowledge should positively impact on the development of vaccine formulations and intervention strategies for improved control of enteric infections in developing countries. Registration fees # The Registration Fee is $715.00 on and before September 7, 2011. # After September 7, 2011, the ...
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 ...
The Thomsen-Friedenreich (T) antigen, #betta#-D-Gal-(1->3)-#alpha#-D-GalNAc, is exposed in reactive form on many human adenocarcinomata, but not on corresponding benign tissues. Peanut lectin (PNA) has a strong binding affinity for the T antigen and reportedly binds preferentially to certain malignant tissues. We investigated the potential of radio-labelled PNA as a tumour localising agent in an animal model system using a mouse lymphoma (RI) shown to bind fluorescein-labelled PNA in vitro. The radio-iodinated lectin showed good tumour localisation and rapid blood clearance. Clear images of tumours were obtained, in serial scintigraphic imaging, by 24 and 48 h. No blood background subtraction was necessary. Biodistribution studies revealed tumour to blood ratios in mice were 6:1 (at 24 h) and 17:1 (at 48 h), and tumour to muscle ratios were 34:1 (at 24 h) and 40:1 (at 48 h). Rapid in vivo breakdown of _1_2_5I-PNA led to some localisation of ...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...
Monoclonal antibodies (MAbs) 19-9 and 73-3 specific for human colon adenocarcinoma were labelled with a high number of gadolinium atoms. Twenty five DTPA were chelated per MAb, with only slight loss of immunoreactivity. The NMR contrast agent Gd-25 DTPA-MAb 19-9 or 73-3 ((Gd) 17 mumole/kg, (MAb) 60 microM) was injected into nude mice bearing human colon adenocarcinoma (SW948). Tumors were removed 24 hr after injection and T1 was measured in vitro. T1 relaxation time varied according to MAb specificity against tumour targets; T1 decreased 20% for MAb 19-9 and MAb 73-3 with SW948 tumor. Imaging was performed with this model. Very good contrast was obtained 24 hr after Gd-25 DTPA-MAb injection.
Through DNA methylation, histone modifications, and small regulatory RNAs the epigenome systematically controls gene expression during development, both in utero and throughout life. The epigenome is also a very reactive system; its labile nature allows it to sense and respond to environmental perturbations to ensure survival during fetal growth. This pliability can lead to aberrant epigenetic modifications that persist into later life and induce numerous disease states. Endocrine-disrupting compounds (EDCs) are ubiquitous chemicals that interfere with growth and development. Several EDCs also interfere with epigenetic programming. The investigation of the epigenotoxic effects of bisphenol A (BPA), an EDC used in the production of plastics and resins, has further raised concern over the impact of EDCs on the epigenome. Using the Agouti viable yellow (A(vy)) mousemodel, dietary BPA exposure was shown to hypomethylate both the A(vy) and the ...
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 mousemodels 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 ...
Correlates between immunological parameters and protection against Bacillus anthracis infection in animals vaccinated with protective antigen (PA)-based vaccines could provide surrogate markers to evaluate the putative protective efficiency of immunization in humans. In previous studies we demonstrated that neutralizing antibody levels serve as correlates for protection in guinea pigs (S. Reuveny et al., Infect. Immun. 69:2888-2893, 2001; H. Marcus et al., Infect. Immun. 72:3471-3477, 2004). In this study we evaluated similar correlates for protection by active and passive immunization of New Zealand White rabbits. Full immunization and partial immunization were achieved by single and multiple injections of standard and diluted doses of a PA-based vaccine. Passive immunization was carried out by injection of immune sera from rabbits vaccinated with PA-based vaccine prior to ...
In this paper we present an overview of the literature on efficacy and safety trials of the various pneumococcal conjugate vaccines on the market (PCV7) and in development (PCV9, PCV11 and allegedly PCV10 and PCV13), as well as of observations from post-licensure studies. Seven- (PCV7) and nine-valent PCV (PCV9) are reported to be sufficiently immunogenic after administration of a 3+1 schedule in infants in various RCTs. PncOMPC (PCV7 with a protein of N. meningitidis as a carrier) is less immunogenic, though this may have no repercussions for the protective efficacy against clinical disease. PCV7 is 82-97% efficacious against vaccine serotype (VT) IPD, 90% efficacious against (clinically diagnosed) pneumococcal pneumonia, and, like the 11-valent PCV, 57% efficacious against VT acute otitis media. Naturally, it would be of paramount public health interest if the same levels of efficacy and effectiveness could be achieved with fewer doses. ...
Deer Elk Bighorn Sheep American Pronghorn Moose Deer Mouse Carnivores Bobcat American Badger River Otter Red Fox Long-Tailed Weasel Coyote Grizzly Bear Mountain Lion Amphibians...
Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics...Full Text Available
The extent (density and diameter) of the native (preexisting) collateral circulation in healthy tissues and the capacity of collaterals to enlarge/remodel in obstructive arterial disease are important...Full Text Available
In mammals, primordial germ cells (PGCs) are generated in the extra-embryonic epiblast, and thereafter migrate into the developing gonads. Following the development of the gonads to the testes or ovaries, germ cells mature into sperms or eggs. In the present study, we report production and characterization of monoclonal antibodies (MAb) that recognize PGCs. Extracts from E12.5 mouse embryonic gonads were immunized as an antigen, and hybridomas were generated using the rat medial iliac lymph node method. The hybridoma supernatants were screened by immunohistochemical analyses of E12.5 mouse embryonic sections. The antibody, referred to herein as MAb 5B5, provided strong signals on PGCs. Moreover, immunofluorescence analyses using a variety of the tissue sections of mouse embryos revealed th...
These proceedings collect papers on the subject of lymphokines. Topics include: DNA-cloning of mouse and human lymphokine genes, inteferons, interleukins, gene expression, tumor necrosis factors, and recombinant DNA.
... accidentally released from a Soviet military laboratory (Meselson ... Robert Koch and Louis Pasteur worked to introduce ... species (eg, rat, mouse, dog, monkey) for ...
The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not bind to soluble and ...
Two monoclonal antibodies, TAL-1B5 and TAL-3C3, specific for human Ia alpha-chain subunits have been produced by fusing P3/NSI/1-Ag4-1 mouse myeloma cells with spleen cells from a BALB/c mouse immunized...Full Text Available
Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived...Full Text Available
Cadmium (Cd) exposure causes glucosuria (glucose in the urine). Previously, it was shown that Cd exposure of primary cultures of mouse kidney cells (PMKC) decreased mRNA levels of the glucose...Full Text Available
Data from 52 litters farrowed in two seasons of a cross-fostering experiment were analyzed to estimate variances and covariances for additive direct and maternal genetic effects on immune response to pseudorabies virus and B. bronchiseptica vaccine. Twenty purebred boars and 44 sows of the Duroc, Landrace and Yorkshire breeds were used. Immune response was measured after vaccine challenge. A modified-live pseudorabies (PR) vaccine was administered to piglets at 28 d of age; response was measured by log2 serum neutralization titers at 56 d. An inactivated B. bronchiseptica bacterin was administered at 28, 42 and 112 d. Antibody levels were measured relative to positive and negative controls at 28, 56 and 119 d by using an enzyme-linked immunosorbent assay (ELISA). Results from this study for heritability were .18 +/- .09 for PR titer and .15 +/- .07 and .52 +/- .15 for 56- and 119-d ELISA values, respectively. The ...
The human smooth muscle myosin heavy chain locus (MYH11) was mapped by fluorescence in situ hybridization to the middle of the p arm of chromosome 16 using a genomic cosmid clone containing coding sequences of the gene as probe. Probe from coding sequence, when applied to Southern blots of a panel of hybrids containing different portions of human chromosome 16, localized the gene to 16p13.13-13.12. Coding sequence PCR primers, when used on the DNA from a CHO-mouse hybrid clone mapping panel informative for mouse chromosomes, showed that the gene was located on mouse chromosome 16. These results correct a recent assignment of MYH11 from 16q12.2 to the region of the 16p-arm inversion breakpoint seen in acute myelomonocytic leukemia (AMML) M4Eo and demonstrate that the conflicting data do not result from the presence of additional MYH genes on the q arm of the chromosome. Also, a new region of conserved synteny between human ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that factor(s) in the mouse ...
All Streptococcus pneumoniae strains isolated from paediatric clinical samples at Heraklion University General Hospital in the 10-year period 2000-2009 were tested for serotype and susceptibility to antimicrobials. Among a total of 258 strains, 159 were isolated in the 5-year period 2000-2004, before the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7), and 99 in the post-PCV7 5-year period 2005-2009. The prevalence of PCV7-included serotypes decreased in the post-PCV7 period (p?=?0.0002), but an increase was observed for serotypes 7F (p?=?0.002) and 19A (p?=?0.004). Pan-susceptibility rates and susceptibility to cotrimoxazole increased in the post-PCV7 period (p?=?0.01 and p?=?0.008, respectively), but serotype 19A emerged as a contributor to multi-resistance (p?=?0.007). PCV7 was followed by decreased S. pneumoniae resistance and prevalence of vaccine-related serotypes but increased prevalence of serotypes 7F and 19A. ...
Based on studies on the genetic and molecular basis of Shigella flexneri invasive properties, we have constructed and evaluated a double mutant of S. flexneri serotype 5 for utilization as a live attenuated oral vaccine against shigellosis. The first mutation, icsA, blocks intracellular spread of bacteria as well as cell-to-cell infection. It affects the capacity of the invasive pathogen to form large abscesses in epithelia. The second mutation, iuc, eliminates production of the siderophore aerobactin thus impairing growth of the bacterium within tissues. This double mutant, SC5700 appeared safe when administered intragastrically to macaque monkeys as three doses (5 x 10(10) c.f.u. each) at weekly intervals. Protection against a challenge by the wild type isolate (M90T) was observed 4 weeks after the last vaccine inoculation. Duration of carriage was considerably reduced as compared to the control group in which all animals had developed severe ...
European sea bass (Dicentrarchus labrax L.) is a marine species of great economic importance, particularly in Mediterranean aquaculture. However, numerous pathogenic viruses, bacteria, fungi and parasites affect the species, causing various infectious diseases and thereby leading to the most heavy losses in aquaculture production of sea bass. In this respect, knowledge on molecular and genetic mechanisms of resistance to pathogens and specific features of immune response against various infectious agents should greatly benefit the development of effective vaccines and proper vaccination strategies in marker-assisted selection of fish resistant to a range of infections. To date, genetic knowledge on sea bass immune regulatory genes responsible for resistance to pathogens is relatively poor ...
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...
AbstractBackground Randomised controlled trials (RCTs) in the 1970s and early 1980s showed the polysaccharide serogroup A vaccine (SgAV) prevented serogroup A meningococcal meningitis (SGAMM). Subsequent non-RCTs suggested significant variations in the age-specific duration of protection among children. Objectives To determine the protective effect, duration of protection, age-specific effects and the effect of booster doses in children of the SgAV against SGAMM. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1950 to May Week 3, 2010) and EMBASE (January 1974 to May 2010). Selection criteria We included RCTs. Non-RCTs ...
Full text: The general population is daily exposed to chronic, low doses of ionizing radiation (IR) from both natural and artificial sources. The biological consequences of acute, high dose IR exposure can be readily determined; however, the nature and significance of low dose, low dose-rate IR effects are still the subject of debate. Confounding the issue, are the phenomena collectively referred to as the Radiation-induced Bystander Effect (RIBE). The RIBE describes a collection of in vitro observations that suggest the presence of a soluble, transmissible factor(s) released from irradiated cells that can induce a biological response in un-irradiated cells. The induction, nature and magnitude of the RIBE varies between cell culture systems, radiation sources and end-points measured. Efforts to confirm the presence of the RIBE in vivo have been confined to in vivo-like culture systems and limited work with tumour and bone-marrow transplantation models. Validation ...
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 ...
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).
Hepatitis B subviral particles, purified from plasma of asymptomatic carriers seropositive for hepatitis B e antigen, were treated with various conditions reported for the processing of vaccines. Thereafter,...Full Text Available
Serum and salivary responses of 95 infants to either a standard (4 x 10(4) plaque-forming units (PFU), 47 neonates) or a high dose (4 x 10(5) PFU, 48 neonates) of tetravalent reassortant rhesus rotavirus...Full Text Available
The ERA strain of rabies virus was propagated in a baby hamster kidney cell line (BHK-21/C13). The viral titer was 10(1.8) tissue culture infective doses (TCID) higher than that of commercial ERA vaccine....Full Text Available
To assess the influence of a live attenuated oral vaccine against porcine post-weaning colibacillosis (PWC) induced by enterotoxigenic Escherichia coli (ETEC) on mucosal lymphoid cell CD45 isoforms expression, experimental group of weaned pigs (n=6) was immunized orally with F4ac+ non-ETEC strain (day 0) and challenged with F4ac+ ETEC strain 7 days latter. Non-immunized ETEC-infected pigs (n=6) served as control. All pigs were killed on post-challenge day 7. The small intestine was excised for isolation of jejunal lamina propria (JLP) and ileal Peyer's patch (IPP) lymphocytes and immunohistochemical studies. The results obtained by immunophenotyping of isolated cells show that the proportion of CD45RA+ and CD45RC+ JLP, but not IPP, cells were higher in the non-ETEC-immunized ETEC-infected pigs versus non-immunized infected. Additionally, while CD45RA+ JLP cells increased only slightly, the expression of CD45RC isoform on the JLP cells was significantly higher ...
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 examined is suitable for use in a human oral ...
Newly hatched chicks were dosed orally with a Salmonella typhimurium wild-type strain, an S. enteritidis wild-type strain, and a genetically defined S. enteritidis aroA vaccine candidate, strain CVL30....Full Text Available
Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-β to adjuvant the response to a rabies virus...Full Text Available
BackgroundAfrican horse sickness virus (AHSV) causes a non-contagious, infectious disease in equids, with mortality rates that can exceed 90% in susceptible horse populations....Full Text Available
Among important candidates for babesial vaccines are apical complex proteins, including rhoptry-associated protein 1 (RAP-1) from Babesia bovis and B. bigemina, which...Full Text Available
A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of...Full Text Available
In order to conserve vaccines in hot countries a solar refrigerator has been made by a French university. It is a photothermal refrigerator without batteries. It uses two gases: ammonia and calcium chloride. The refrigerator is autonomous and can work eleven days without sun. (N.C.)
Advances in laboratory animal imaging have provided new resources for noninvasive biomedical research. Among these technologies is microcomputed tomography (microCT) which is widely used to obtain high...Full Text Available
BackgroundXenotropic Murine Leukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study,...Full Text Available
As part of a combined study of the responses of the mouse adrenal gland and kidney to X-irradiation, the weight of adrenal glands, the relative volumes of the cortex and medulla and the aldosterone output were measured at predetermined times after irradiation of the left organs only.
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...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
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged ...
... from Dr. Austin Smith of the Institute for Stem Cell Research, University of Edinburgh) was modified from the CGR8 ... to thank Dr. Austin Smith, the Institute for Stem Cell Research, University of Edinbu...
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
We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated...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
Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was...Full Text Available
Vulnerability to abused drugs is influenced by multiple genes unique to each drug as well as to risk genes for polydrug abuse. If several inbred mouse strains respond to different drugs similarly,...Full Text Available
The integration sites for viral DNA in cells infected with Moloney murine leukemia virus (M-MuLV) were studied by restriction endonuclease cleavage of cellular DNA followed by electrophoresis in agarose...Full Text Available
PurposeThe size of neuronal populations is modulated by gene variants that influence cell production and survival, in turn influencing neuronal connectivity, function,...Full Text Available
BackgroundMacrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized...Full Text Available
The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...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
There is increasing consensus that the uterotrophic estrogenicity assay should be coupled with other morphometric or molecular end points that might enhance its sensitivity. We have previously shown...Full Text Available
Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human...Full Text Available
BackgroundThe zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In...Full Text Available
BackgroundRecessive mutations in guanylate cyclase-1 (Gucy2d) are associated with severe, early onset Leber congenital amaurosis-1(LCA1). Gucy2d...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
BackgroundBrevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in...Full Text Available
In the present study we have used the alkaline elution technique to study the effect of misonidazole (MISO) on the initial amount of DNA cross-linking in various normal and neoplastic tissues of C3H...Full Text Available
During asymmetric mitosis, both in male Drosophila germline stem cells and in mouse embryo neural progenitors, the mother centrosome is retained by the self-renewed cell; hence suggesting...Full Text Available
BackgroundDiurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling...Full Text Available
While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here...Full Text Available
Oocyte-cumulus cell bidirectional communication is essential for normal development of the oocyte and cumulus cells (CCs) within the follicle. We showed recently that addition of recombinant growth...Full Text Available
NG2 chondroitin sulfate proteoglycan is a surface marker of oligodendroglial progenitor cells (OPCs) in various species. In contrast to well-studied rat OPCs, however, we found that purified...Full Text Available
A novel therapeutic compound was found to induce bladder tumors in male rats. Given the location of the tumors and the increased amounts of calcium- and magnesium-containing solids found in the urine...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
OBJECTIVEPrevious studies showed that genetic deletion or pharmacological blockade of the receptor for advanced glycation end products (RAGE) prevents the early structural changes...Full Text Available
Self-renewal of spermatogonial stem cells (SSCs) is the foundation for maintenance of spermatogenesis throughout life in males and for continuation of a species. The molecular mechanism underlying stem...Full Text Available
BackgroundMammalian antimicrobial peptides (AMPs) are effectors of the innate immune response. A multitude of signals coming from pathways of mammalian pathogen/pattern recognition...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
We report the isolation of cDNA clones for the mouse {alpha}7 neuronal nicotinic acetylcholine receptor subunit (gene symbol Acra7), the only nicotinic receptor subunit known to bind a-bungarotoxin in mammalian brain. This gene may have relevance to nicotine sensitivity and to some electrophysiologic findings in schizophrenia. The mouse {alpha}7 subunit gene encodes a protein of 502 amino acids with substantial identity to the rat (99.6%), human (92.8%), and chicken (87.5%) amino acid sequences. The {alpha}7 gene was mapped to mouse chromosome 7 near the p locus with the following gene order from proximal to distal: Myod1-3.5 {+-}1.7 cM-Gas2-0.9 cM {+-} 0.9 cM-D7Mit70-1.8 {+-} 1.2 cM- Acra7-4.4 {+-}1.0 cM-Hras1-ps11/Igf1r/Snrp2a. The human gene was confirmed to map to the homologous region of human chromosome 15q13-q14. 26 refs., 3 figs.
During blastocyst formation the segregation of the inner cell mass (ICM) and trophectoderm is governed by the mutually antagonistic effects of the transcription factors Oct4 and Cdx2. Evidence indicates...Full Text Available
We sought to determine the effects of activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) on multilocularization of adipocytes in adult white adipose tissue (WAT). Male...Full Text Available
BackgroundA fundamental requirement for the exploitation of embryonic stem (ES) cells in regenerative medicine is the ability to reproducibly derive sufficient numbers of cells of...Full Text Available
Cultured mouse or human embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Chemical or insertional...Full Text Available
Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified...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 ...
Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. Heterologous ...
A Task Group of the International Commission on Radiological Protection (ICRP) has finished a report Biological Effects after Prenatal Irradiation (Embryo and Fetus) which has been approved by the Main Commission and Will be Published. Some new important scientific data shall be discussed in this contribution. During the preimplantation period lethality of the mammalian embryo is the dominating radiation effect. However, in mouse strains with genetic predispositions it has been shown that also malformations can be caused. This effect is genetically determined and its mechanisms is different from the induction of malformations during major organogenesis. Radiation exposures during this prenatal period leads ato an increase of genomic instability of cells in the normal appearing fetuses. These radiation effects can be transmitted to the next generation. A renewed analysis of individuals with severe mental retardation after exposures during the 8th to 15th week post ...
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 mousemodel beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and ...
Survival curves were constructed from dose-incidence curves for apoptosis in the crypts of mouse small intestine, using the number of apoptotic cells after high doses (N{sub M}) as maximum cell population size. The mean lethal doses (D{sub 0}) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both D{sub 0} and N{sub M} values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. (author).
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 ...
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 injection (10"1"0 vp) of the replication-competent ...
Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the calculation of the absorbed ...
Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the...
There is very little known about the long-term evolution of the MHC and MHC-like molecules. This is because both the theory (the evolutionary questions and models) and the practice (the animals systems, functional assays and reagents to identify and characterize these molecules) have been difficult to develop. There is no molecular evidence yet to decide whether vertebrate immune systems (and particularly the MHC molecules) are evolutionarily related to invertebrate allorecognition systems, and the functional evidence can be interpreted either way. Even among the vertebrates, there is great heterogeneity in the quality and quantity of the immune response. The functional evidence for T-lymphocyte function in jawless and cartilagenous fish is poor, while the bony fish seem to have many characteristics of a mammalian immune system. The organization and sequence of fish Ig genes also indicate that important events in the evolution of the immune system and the MHC ...
Full text: An adaptive response is a decreased biological effect induced by a priming radiation dose given prior to a challenge dose. Adaptive responses contradict the linear-nothreshold model of risk estimation. The pKZ1 mouse chromosomal inversion assay is an extremely sensitive assay for studying the mutagenic effect of low dose radiation. A non-linear dose response for chromosomal inversion has been observed in pKZ1 spleen and prostate after a single whole body irradiation with doses between 1?Gy and 10mGy. Doses between 5-10?Gy resulted in an induction in inversions and doses between 1-10mGy resulted in a reduction below endogenous inversion frequency. These results suggest that doses in the 1-10 mGy range cause host responses which overcompensate by not only preventing inversions that would normally occur as a result of the low doses of radiation but also by preventing some of the endogenous inversions that would have occurred in the ...
We cloned and characterized horse preproendothelin-2 (PPET-2) cDNA from intestinal tissue. The cDNA encoded 178 amino acids of the PPET-2 polypeptide, in which a 21-amino-acid mature endothelin-2 peptide and a 16-amino acid endothelin-2-like peptide were found. For the open reading frame the correspondence of horse PPET-2 cDNA with those of the ferret, human, dog, mouse and rat was 85.1%, 84.9%, 82.1%, 77.8% and 77.2%, respectively. Analysis of the organ distribution of PPET-2 mRNA by reverse transcription-polymerase chain reaction demonstrated that the kidney, stomach and small intestine are major sites of expression of the PPET-2 gene. Surprisingly, the mRNA is not detected in the large intestine, where high expression is demonstrated in the mouse and rat. This difference may result from the underlying functional differences of the large intestine between a herbivore (horse) and an omnivore (mouse and rat). PMID:15838341
Yeast artificial chromosome (YAC) libraries have been difficult to construct with average insert sizes >400 kilobase pairs when DNA is size-fractionated in low-melting-point agarose. By using yeast chromosomes in mock cloning experiments, the authors found that polyamines should be present whenever agarose containing high molecular weight DNA is melted to protect DNA from degradation. By incorporating polyamines during the cloning procedure, they constructed YAC libraries from mouse and human DNA with average insert sizes of 700 and 620 kilobase pairs, respectively. Several genome equivalents of these YAC libraries were replicated onto the surface of many duplicate agar plates using a 40,000 multipin transfer device. High-density filter replicas were screened by hybridization, and 70 mouse YAC clones from 31 loci and 132 human YAC clones from 49 loci were isolated.
In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci. Offspring were analyzed for hemoglobin properties (electrophoretic pattern, solubility, crystal pattern), serum albumin differences, erythrocyte lysis, reticulocyte count, and external appearance. Five hemoglobin variants were found among the mutants. In three, the genetic contribution from the irradiated father was not expressed with regard to the #alpha#-chain; one carried a tandem duplication (the first known case in the mouse) involving Hbb; and one probably resulted from double nondisjunction of chromosome 7. The finding that major chromosome aberratios can mimic hemoglobin mutations indicates the need, in similar experiments, to follow F_1 screening with thorough cytogenetic analysis. The ...
Objective: To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1@a,25(OH)"2D"3 or soluble receptor activator of nuclear factor-@kB ligand (s-RANKL). Materials and methods: Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10%) and tetracyclines (2.5, 5 and 10@mM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1@a,25(OH)"2D"3 (10nM) or s-RANKL (20ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1@a,25(OH)"2D"3 or s-R...
The yellow Iranian scorpion Odontobuthus doriae can cause fatal envenoming, but its mechanism of action is unclear. One of the reported manifestations of envenoming is moderate to severe involuntary tremor of skeletal muscle. In order to understand better the mechanism of action of this venom on skeletal muscle function, we examined the effects of the venom in vitro on chick biventer cervicis (CBC) and mouse hemidiaphragm (MHD) nerve muscle preparations. O. doriae venom (0.3-10mg/ml) initially increased and then decreased twitch height. The venom also caused contracture in both preparations. In mouse triangularis sterni preparations, used for all intracellular recording techniques, the venom enhanced the release of acetylcholine and induced repetitive firing of nerve action potentials and ...
The present study was aimed at investigating effects of nickel (NiCl2) on secretion of testosterone (T), cell viability, ultrastructure and apoptosis in mouse Leydig cells. Testosterone release was measured after 48h of culture with 15.67, 31.25, 62.5, 125, 250, 500 and 1000mmol/L NiCl2 or without NiCl2 using radioimmunoassay. Cell viability was assessed by a MTT (metabolic activity assay). Quantification of apoptotic cells was performed using TUNEL assay and the ultrastructural changes were analyzed using transmission electron microscopy. The viability was decreased after addition of >=250mmol/L NiCl2. A concentration-dependent depression of T production was observed. The percentage of apoptotic cells was significantly increased only after addition of 125, 250 and 1000mmol/L NiCl2. After ...
The 50th anniversary of Mary Lyon?s 1961 Nature paper, proposing random inactivation in early embryonic life of one of the two X chromosomes in the cells of mammalian females, provides an opportunity to remember and celebrate the work of those involved. While the hypothesis was initially put forward by Lyon based on findings in the mouse, it was founded on earlier studies, notably the work of Susumu Ohno; it was also suggested independently by Beutler and colleagues using experimental evidence from a human X-linked disorder, glucose-6-phosphate dehydrogenase deficiency, and has proved to be of as great importance for human and medical genetics as it has for general mammalian genetics. Alongside the hypothesis itself, previous cytological studies of mouse and human chromosomes, and the obse...
Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor...
The expression of motor activity levels in response to novel situations is under complex genetic and environmental control. Several genetic loci have been implicated in the regulation of this behavioral phenotype, but their relationship to epigenetic and epistatic interactions is relatively unknown. Here, we report on a quantitative trait locus (QTL) on mouse chromosome 1 for novelty-induced motor activity in the open field, using chromosome substitution strains derived from a high active host strain (C57BL/6J) and a low active donor strain (A/J). The QTL for open field (horizontal distance moved) peaked at the location of Kcnj9, however, QTL detection was initially masked by an interplay of both grandparent genetic origin and genetic co-factors influencing behavior on chromosome 1. Our fi...
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...
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.
c-Jun N-terminal kinase 2 (JNK2) isoforms are transcribed from the jnk2 gene and are highly homologous with jnk1 and jnk3 transcriptional products....Full Text Available
Hypoxia causes abnormal neonatal pulmonary artery remodeling (PAR) and inhibition of alveolar development (IAD). Transforming growth factor (TGF)-β is an important regulator of lung development...Full Text Available
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
RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also...Full Text Available
Stearoyl-coenzyme A desaturase (SCD) is the rate-limiting enzyme necessary for the biosynthesis of monounsaturated fatty acids. In this study, we investigated the regulation of mouse SCD1 by liver X...Full Text Available
We present a drawing package optimised for Feynman diagrams. These can be constructed interactively with a mouse-driven graphical interface or from a script file, more suitable to work with a diagram generator. It provides most features encountered in Feynman diagrams and allows to modify every part of a diagram after its creation. Special attention has been paid to obtain a high quality printout as easily as possible. This package is written in Tcl/Tk and in C. (orig.).
Two cellular DNA regions representing common domains for proviral DNA integration ( Mlvi -1 and Mlvi -2) have been identified in Moloney murine leukemia virus-induced rat thymic lymphomas. Cellular...Full Text Available
Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available
4.5S RNA is a group of RNAs 90 to 94 nucleotides long (length polymorphism due to a varying number of UMP residues at the 3' end) that form hydrogen bonds with poly(A)-terminated RNAs isolated from...Full Text Available
Abstract Development of inhibitors and vaccines that mitigate rumen-derived methane by targeting methanogens relies on knowledge of the methanogens present. We investigated the composition of archaeal communities in the rumens of farmed sheep (Ovis aries), cattle (Bos taurus) and red deer (Cervus elaphus) using denaturing gradient gel electrophoresis (DGGE) to generate fingerprints of archaeal 16S rRNA genes. The total archaeal communities were relatively constant across species and diets, and were less variable and less diverse than bacterial communities. There were diet- and ruminant-species-based differences in archaeal community structure, but the same dominant archaea were present in all rumens. These were members of three coherent clades: species related to Methanobrevibacter ruminan...
The efficiency of dendrosome (a gene porter) was assessed in transferring recombinant human rotavirus VP2 cDNA into A549, a human lung cell line. After gene transferring, transmission electron microscopy showed core-like particles (CLPs) formation in the transfected cells both with dendrosome and lipofectamine porters. In addition, western blotting analysis showed that the expression of VP2 gene was almost equal in the dendrosome and lipofectamine-transfected cells. Also, the cytotoxicity studies revealed that dendrosome had a lower cytotoxicity than lipofectamine. Therefore, our study may introduce dendrosome as a possible carrier for gene transferring into the human lung cell line, especially, for intranasally administration of DNA vaccines.
Mycoplasma ovipneumoniae is associated with chronic non-progressive pneumonia of sheep and goats. As with many other mycoplasmas involved in animal diseases, protective immune responses have not been achieved with vaccines, even though antibody responses can be obtained. This study focuses on characterizing the interaction of M. ovipneumoniae with ovine PBMC using carboxy-fluorescein-succinimidyl-ester (CFSE) loading and flow cytometry to measure lymphoid cell division. M. ovipneumoniae induced a strong in vitro polyclonal suppression of CD4^+, CD8^+, and B blood lymphocyte subsets. The suppressive activity could be destroyed by heating to 60^oC, and partially impaired by formalin and binary ethyleneimine treatment that abolished its viability. The activity resided on the surface-exposed m...
Three in vivo assays were used to measure the immunocompetence of chickens in two generations of a selection experiment. The obtained data were used to estimate the variance components for sire and dam for antibody production to Pasteurella multocida and Mycoplasma gallisepticum vaccines, for T-cell-mediated immunity evaluated by a phytohemagglutinin wing web assay, and for clearance of foreign particles from the circulatory system. Heritabilities of and genetic correlations among these immunological traits were calculated from the sire variance components. Heritability estimates of the immunological traits based on the sire component of variance ranged from .06 to .53, and genetic correlations among immunological traits were generally negative. PMID:1956847
Chitosan (a?-(1-4)-amino-2-deoxy-b?-D-glucan) is a deacetylated form of chitin, a polysaccharide from crustacean shells. Its unique characteristics, such as positive charge, biodegradability, biocompatibility, nontoxicity, and rigid structure, make this macromolecule ideal for an oral vaccine delivery system. We prepared reverse-phase evaporation vesicles (REVs) sandwiched by chitosan (Chi) and polyvinylic alcohol (PVA). However, in this method, there are still some problems to be circumvented related to protein stabilization. During the inverted micelle phase of protein nanoencapsulation, hydrophobic interfaces are expanded, leading to interfacial adsorption, followed by protein unfolding and aggregation. Here, spectroscopic and immunological techniques were used to ascertain the effects ...
Brucella melitensis is a Gram-negative coccobacillus bacteria belonging to the Alphaproteobacteria subclass. It is an important zoonotic pathogen that causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. The B. melitensis strain M5-90, a live attenuated vaccine cultured from the B. melitensis virulent strain M28, has been an effective tool to control brucellosis in goats and sheep in China. Here we report the complete genome sequences of B. melitensis M28 and M5-90, strains with different virulence backgrounds, which will serve as a valuable reference for future studies. PMID:21478357
Background: Chloroquine has in-vitro activity against influenza and could be an ideal candidate for worldwide prevention of influenza in the period between onset of a pandemic with a virulent influenza strain and the development and widespread dissemination of an effective vaccine. We aimed to assess the efficacy of such an intervention. Methods: In this randomised, double-blind, placebo-controlled trial done at a single centre in Singapore, we randomly assigned (1:1) healthy adults to receive chloroquine phosphate (500 mg/day for 1 week, then once a week to complete 12 weeks) or matching placebo by use of a computer-generated randomisation list. Participants filled an online symptom diary every week, supplemented by daily diaries and self-administered nasal swabs when unwell. Haemagglutin...
Summary The antigenic relationship between the phocine distemper virus (PDV) strain causing the epidemic in 2002 and the PDV strain of 1988, canine distemper virus from two dogs and one marten, and one measles virus strain was investigated in vivo and in vitro using monospecific polyclonal and monoclonal antibodies directed against five different proteins of canine or phocine distemper virus (N, P, M, F, H). Epitopic mapping revealed no difference between the PDV strains causing the epidemics in 1988 or 2002. However, the use of these antibodies allowed discrimination between different morbilliviruses including a vaccine strain of canine distemper virus. The major differences among the investigated morbilliviruses were found in the H protein.
Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103. 36 refs., 6 figs., 1 tab.
The purpose was to study the toxicity of drugs known to generate free radicals on isolated pancreatic islets. The accumulattion of "8"6Rb"+ by mouse pancreatic islets was measured in vitro. Exposing the islets to 6-hydroxydopamine, minhydrin, or phenazine methosulphate + NADH inhibited the Rb"+ uptake, whereas paraquat or acetylphenylhydrazine had no effect. This effect of 6-hydroxydopamine was prevented by either of the hydroxyl radical scavengers, sodium benzoate and mannitol, but not by the non-scavenger,urea; ninhydrin was partially protected against by mannitol but not by benzoate. Protection against 6-hydroxydopamine was also afforded by D-glucose but not by L-glucose or 3-O-methyl-D-glucose; none of the sugars protected against ninhydrin. In damaging islet beta-cells and in being protected against by D-glucose, 6-hydroxydopamine closely resembles the diabetogenic drug, alloxan. It is suggested that protection against alloxan may involve both glucose ...
Results reported are for single dose exposures and refer to "6"0Co-#gamma#-irradiation. The RBE determined by V79 cell survival and based on the Do ratio was found to be 1.70#+-#0.4 ranging from 1.5 to 1.8. In the case of the regeneration of mouse jejunal crypts the RBE was calculated at ten cell curvival and was found to be 1.68. The maximum acute mouse skin reaction at a skin score of 2.0 was found to be 2.1 while the average skin reaction was 1.7. Growth retardation of Vicia faba bean roots measured at the level of 50% indicated an average RBE of 3.0 and a range of 2.7 to 3.7. The OER obtained for V79 cell survival was found to be 1.7 to 1.8. Comparison is made with the RBE and OER measurements for the neutron facilities at Clatterbridge, Fermilab and Louvain-la-Neuve which produce neutrons by the same nuclear reaction and whose physical specifications closely resemeble those of the Faure neutrons. This comparison indicates that the Faure ...
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 endpoint measured. ...
Goosecoid is a homeobox gene first isolated from a Xenopus dorsal lip cDNA library. Homologous genes have been isolated from mouse, zebrafish, and chick. In all species examined, the gene is expressed and plays an important role during the process of gastrulation in early embryonic development. The authors report here the cloning of the human goosecoid (GSC) from a genomic library and the sequence of its encoded protein. The genomic organization and protein sequence of the human gene are highly conserved with respect to those of its Xenopus and mouse counterparts: all three genes consist of three exons, with conserved exon-intron boundaries. The sequence of the homeo-domain is 100% conserved in most vertebrates. Using somatic cell hybrid and chromosomal in situ hybridization, the gene was mapped to chromosome 14q32.1. 30 refs., 3 figs., 2 tabs.
Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of ...
Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also ...
The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity of ETB was localized to the myenteric plexus. These findings ...
We have been investigating radiation-induced neoplastic transformants of C3H 10T1/2 mouse fibroblasts for evidence of heritable changes. C3H 10T1/2 cells were treated with 8 Gy X rays. After approximately 8 weeks of culture, type II/III foci were isolated from the monolayer using cloning rings. Cell lines developed from these foci, and clones established from these cell lines, were examined for DNA content. The isolated focus-derived populations and derived clones often display aneuploidy and/or polyploidization. In one instance a clone (derived from a single cell) displayed multiple polyploidies. During passage the ploidy of many of the anomalous populations gradually reverted to the ploidy of the non-neoplastically transformed state. The morphological features associated with the neoplastic transformation event were nevertheless retained. The results demonstrate that exposure to radiation can induce, in association with morphological neoplastic transformation, a ...
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 amoebic strains are of ...
The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at ...
Thymic epithelial cells (TECs) constitute a major component of the thymic stroma which provides a microenvironment critical for developing thymocytes. We have previously demonstrated that doxycycline (Dox), a tetracycline derivative, enhances the proliferation of the mouse thymic epithelial cell line 1 (MTEC1) via MAPK/ERK signal pathway. Herein we provide evidence that Dox also has profound impact on the cytokine production by MTEC1. Specifically, the expression of IL-6 and GM-CSF, both at mRNA and protein levels, was found to be increased in a time- and dose-dependent manner with the addition of Dox. Western blotting analysis revealed that treatment with Dox-induced phosphorylation of the p65 subunit of NF-kB and ERK. Notably, Dox-induced up-regulation of IL-6 and GM-CSF was largely abol...
WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.
The photobiology of mouse melanocyte lines with different pigment genotypes was studied by measuring colony-forming ability after irradiation. The cell lines were wild-type black (melan-a) and the mutants brown (melan-b) and albino (melan-c). Four lamps emitting various UV wavelengths were used. These were germicidal (UVC, 200-280 nm), 82.3% output at 254 nm, TL01 (UVB, 280-320 nm), 64.2% at 310-311 nm, FS20, broadband with peak output at 312 nm and Alisun-S (UVA, 320-400 nm), broadband with peak output at 350-354 nm. Appropriate filtration reduced the contaminating UVC to nonlethal levels for the longer waverange lamps. It is clear from these studies that, in pigment cells, monochromatic results cannot predict polychromatic responses and that cell death from solar irradiations is a complex phenomenon that depends on more than DNA damage. (author).
The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.
Hyaluronate (HA) distribution patterns were examined in the cranial mesenchyme underlying the mesencephalic neural folds of mouse embryos maintained in roller tube culture. Using standard image-processing techniques, the digitized images of Alcian blue-stained or 3H-glucosamine-labeled sections digested with an enzyme specific for HA, were subtracted from adjacent, undigested sections. The resultant difference picture images (DPI) accurately depicted the distribution of stained or labeled HA within the cranial mesenchyme. 3H-glucosamine-labeled HA was distributed uniformly throughout the cranial mesenchyme as 12, 18, and 24 hr of culture. By contrast, the mesenchyme was uniformly stained with Alcian blue at 12 hr, but stain intensity decreased in the central regions of the mesenchyme at 18 and 24 hr. HA distribution patterns were also examined in the cranial mesenchyme of embryos cultured in the presence of diazo-oxo-norleucine (DON), a glutamine analogue that ...
We irradiated proton beams on the ears of rabbits and the Harding-Passey mouse melanoma and observed their morphological change. We used 52 MeV proton beams from the INS-FM cyclotron. We adjusted the energy of the proton beams to be at the plateau part of the Bragg curve, at the half-way point of the Bragg peak, and at the Bragg peak. The amount of radiation was 5000rad in each case. The Harding-Passey mouse melanoma was transplanted into the subcutan of a three week old mouse. In this experiment, we used tumors, the diameter of which grew up to 1.5-2cm in 2-3 weeks after the transplantation. Using the jroscope, we observed both lightly and severely damaged cells. Using proton irradiation with the Bragg peak located at depth of 1mm in the rabbit's ears, we studied the change in the tissue. Irradiated epidermis fell off and was eroded because of radiation damage, but the rear surface of the rabbit's ears ...
BackgroundIn recent years, near-infrared fluorescence (NIRF)-labeled iron nanoparticles have been synthesized and applied in a number of applications, including the labeling of human cells for monitoring the engraftment process, imaging tumors, sensoring the in vivo molecular environment surrounding nanoparticles and tracing their in vivo biodistribution. These studies demonstrate that NIRF-labeled iron nanoparticles provide an efficient probe for cell labeling. Furthermore, the in vivo imaging studies show excellent performance of the NIR fluorophores. However, there is a limited selection of NIRF-labeled iron nanoparticles with an optimal wavelength for imaging around 800 nm, where tissue autofluorescence is minimal. Therefore, it is necessary to develop additional alternative NIRF-labeled iron nanoparticles for application in this area.ResultsThis study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, ...
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 ...
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 radioactivity instead, the ...
Medical imaging using single gamma-ray-emitting radionuclides typically makes use of parallel hole collimators or pinholes in order to achieve good spatial resolution. However, a tradeoff in sensitivity is inherent in the use of a collimator, and modern preclinical single photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma rays, often less than 0.1%. A system for small animal SPECT imaging which uses no collimators could potentially achieve very high sensitivity-several tens of percent-with reasonably sized detectors. This would allow two significant improvements in preclinical studies: images could be obtained more rapidly, allowing higher throughput for screening applications, or for dynamic processes to be observed with very good time resolution; and images could be obtained with less radioactive tracer, making possible the in vivo imaging of low-capacity receptor systems, aiding research into new tracer compounds, and reducing the cost ...
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...
Xenotropic murine leukemia virus-related virus (XMRV) was discovered in human prostate tumors and later in some chronic fatigue syndrome (CFS) patients. However, subsequent studies have identified various sources of potential contamination with XMRV and other murine leukemia virus (MLV)-related sequences in test samples. Biological and nucleotide sequence analysis indicates that XMRV is distinct from known xenotropic MLVs and has a broad host range and cell tropism including human cells. Therefore, it is prudent to minimize the risk of human exposure to infection by evaluating XMRV contamination in cell lines handled in laboratory research and particularly those used in the manufacture of biological products. Nested DNA PCR assays were optimized for investigating XMRV gag and env sequences in various cell lines, which included MRC-5, Vero, HEK-293, MDCK, HeLa, and A549, that may be used in the development of some vaccines and other cell lines broadly used in ...
OBJECTIVES: The authors examine the rationale and efficacy of pre-travel hepatitis B immunization strategies based on itinerary and presumed on-travel risk behaviour. METHODS: A large survey among 26,640 Danes survey provided data on journey lengths and destinations, immunization coverage, risk behaviour and knowledge. RESULTS: The estimated cumulative lifetime stay in endemic areas outside Europe is 4.3 months. The majority of risk situations are involuntary and unforeseeable. The majority of risk situations occur on short-term journeys. 5% nonimmune and 5% short-term travellers experienced at least one risk situation such as injections/operations/tattoos on their journey. The level of knowledge of hepatitis A and B is low. CONCLUSIONS: The rationale and efficacy of current immunization strategies are challenged. Based on the results presented here and the availability of vaccines with long-lasting coverage, the authors find that recommendations of immunization ...
1. Gamma globulin metabolism and distribution were studied employing rabbit gamma globulin (RGG)I(131) 24 times in 13 control rabbits. Similar studies were performed before and during the ananmestic response in 4 rabbits previously sensitized with a polyvalent pneumococcal vaccine. 2. During the ananmestic response, gamma-globulin levels increased from 1.0 to 6.0 gm/100 ml, and the gamma-globulin pool increased from 0.7 to 4.7 gm/kg. There was no change in the intravascular-extravascular partition of gamma globulin. 3. Gamma globulin degradation increased from 0.06 to 0.33 gm/kg/day during the 28 days of the immunization period while gamma globulin synthesis increased even further to average 0.47 gm/kg/day. Following the attainment of elevated gamma globulin levels the fractional rate of RGG-I(131) turnover increased from 8.0 to 12.5 per cent/day. 4. No differences were noted in the metabolism of homologous or autologous gamma globulin regardless of the allotypic ...
Hematopoietic stem cells (HSCs) have remained at the forefront of stem cell research for the past 50 years, since the therapeutic potential of bone marrow transplantation was realized. Uniquely, among stem and progenitor cells, research progress has been made in parallel between the laboratory benchtop and hospital bedside during this period. Integral to this work has been the role of the transfusion medicine services in the collection, storage, and processing of HSCs. The next decade promises to bring further developments: with new fields of cellular therapies, stem cell vaccination, and stem cell drug testing opening up. This article summarizes exciting areas of research concerning the behavior and potential clinical applications of HSCs. For the purposes of clarity, we describe in turn the trafficking and transfer of HSCs; ex vivo expansion of HSC units from different sources; and finally, applications of specifically selected subsets of hematopoietic cells and ...
Global meat and milk consumption is exponentially increasing due to population growth, urbanization and changes in lifestyle in the developing world. This is an excellent opportunity for developing countries to improve the livestock sector by using technological advances. Biotechnology is one of the avenues for improved production in the "Livestock revolution". Biotechnology developments applied to livestock health, nutrition, breeding and reproduction are improving with a reasonable pace in developing countries. Simple bio-techniques such as artificial insemination have been well implemented in many parts of the developing world. However, advanced technologies including transgenic plant vaccines, marker assisted selection, solid state fermentation for the production of fibrolytic enzymes, transgenic fodders, embryo transfer and animal cloning are confined largely to research organizations. Some developing countries such as Taiwan, China and Brazil have considered ...
Summary Background Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein 96)-peptide complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma. Methods In this open-label trial, patients were randomly assigned to receive either vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation was done in a one to one ratio by a computer-generated pseudo-random number generator, with a block size of four, and was stratified by performance score, lymph node stat...
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
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...
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 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...
Aims: Rapamycin (sirolimus) is an antibiotic that inhibits protein synthesis through mammalian targeting of rapamycin (mTOR) signaling, and is used as an immunosuppressant in the treatment of organ rejection in transplant recipients. Rapamycin confers preconditioning-like protection against ischemic-reperfusion injury in isolated mouse heart cultures. Our aim was to further define the role of rapamycin in intracellular Ca^2^+ homeostasis and to investigate the mechanism by which rapamycin protects cardiomyocytes from hypoxic damage. Main methods: We demonstrate here that rapamycin protects rat heart cultures from hypoxic-reoxygenation (H/R) damage, as revealed by assays of lactate dehydrogenase (LDH) and creatine kinase (CK) leakage to the medium, by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-d...
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
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...
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for gene therapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current experiments are aimed at determining the extent to which this expansion can occur and whether or not this ...
Many organizations are challenged with the tasks of identifying customer needs and expectations for their products, anticipating future product needs, communicating a future product vision to clients, and designing with today's technology to bring a future vision to successful realization. The design evolution of plant control centres is one aspect of CANDU development that faces such challenges. The Disney Corporation is an example of an organization that has been successful in consistently meeting these challenges for over fifty years; and some of the design practices proven in moviemaking, theme park and resort layout, and vacation experience organization may be helpful and effective when applied in other domains. This paper summarizes the findings from an examination of Disney Corporation design practices, and suggests how some practices could be used to simplify and enhance the design of future CANDU control centres. (author)
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.
We report for the first time a relationship between the Tpl-2/cot oncogene and Mouse Mammary Tumor Virus (MMTV) associated transformation of mammary gland cells. A sub-genomic library generated from a primary mammary gland tumor yielded a novel MMTV integration site which disrupted the Tpl-2/cot proto-oncogene between exons 7 and 8. Comparison of a cell line derived from normal mammary gland (comma-D) and a cell line established from an MMTV induced mammary tumor (GR) demonstrated similar rearrangements within Tpl-2/cot for the GR cells but not in the comma-D cells. These rearrangements in the cell line were accompanied by an increase in the level of Tpl-2/cot specific mRNA. This data suggests that Tpl-2/cot expression may be important in epithelial cell transformation or tumor progression. PMID:8934549
Photoacoustic microscopy (PAM) offers label-free, optical absorption contrast. A high-speed, high-resolution PAM system in an inverted microscope configuration with a laser pulse repetition rate of 100,000 Hz and a stationary ultrasonic transducer was built. Four-dimensional in vivo imaging of microcirculation in mouse skin was achieved at 18 three-dimensional volumes per second with repeated two-dimensional raster scans of 100 by 50 points. The corresponding twodimensional B-scan (50 A-lines) frame rate was 1800 Hz, and the one-dimensional A-scan rate was 90,000 Hz. The lateral resolution is 0.23+/-0.03 ?m for Au nano-wire imaging, which is 2.0 times below the diffraction limit.
Glucagon plays critical roles in regulating glucose homeostasis, mainly by counteracting the effects of insulin. Consequently, the dysregulated glucagon secretion that is evident in type 2 diabetes has significant implications in the pathophysiology of the disease. Glucagon secretion from pancreatic -cells has been suggested to be modulated by blood glucose, signals from the nervous system and endocrine components. In addition to these regulators, intraislet factors acting in a paracrine manner from neighbouring -cells are emerging as central modulator(s) of -cell biology. One of the most important of these paracrine factors, insulin, modulates glucagon secretion. Indeed, the -cell-specific insulin receptor knockout (IRKO) mouse manifests hypersecretion of glucagon in the postprandial stag...
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...
Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...
Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Er...
Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.
XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.5% of patients with CFS [1]. These findings are important because since the initial discovery of XMRV in CFS, several studies have failed to find XMRV in specimens collected from CFS patients. While the current study also did not find XMRV in CFS, Lo et al. did detect sequences that belong to polytropic mouse endogenous retroviruses (PMV), which share considerable similarity with XMRV. Criteria for future studies that will help bring greater clarity to the issue of retroviral sequences in CFS are proposed below. PMID:21994623
In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.
In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.
Amphiphysin is a protein concentrated in neuronal synapses and peripherally associated with neurotransmitter vesicles. It is expressed in many neurons of the central and peripheral nervous systems, in the adrenal medulla, in the anterior and posterior pituitary, in cell lines of the endocrine pancreas, and in spermatocytes. Its subcellular localization and tissue distribution indicate a potential involvement in mechanisms of regulated exocytosis. A role in the dynamic organization of the membrane-associated cytoskeleton is suggested by structural homology to the products of two yeast genes, RVS161 and RVS167, whose mutation results in an abnormal actin distribution, disturbs budding morphology, and impairs cell entry into stationary phase. Limited stretches of sequence similarity, including an SH3 domain, are also shared with other actin-binding proteins. Amphiphysin is the dominant autoantigen in paraneoplastic Stiff-Man syndrome, a neurological autoimmune disorder characterized by ...
The Cox proportional hazards model is the most widely used model for survival analysis because of its simplicity. The fundamental assumption in this model is the proportionality of the hazard function....Full Text Available
PCR detection of genetic material of the parasites present in faeces may be an alternative for microscopic and serological tests routinely used for diagnosing parasitic enteral infections. However, small amount of target DNA combined with low efficiency of total DNA extraction, and presence of PCR inhibitors in the samples to be amplified, may cause false negative detection results. The aim of this work was to evaluate the impact of DNA isolation procedure used on the amplification of DNA fragments from the genomes of protozoan Cryptosporidium parvum and the nematode Trichinella spiralis. Two methods based on different principles of biological material lysis were evaluated; NucliSENS miniMAG employing simultaneously applied chemical lysis and mechanical disruption or mechanical disruption followed by enzymatic lysis in case of QIAamp DNA Stool Mini Kit. Both of the analyzed systems for nucleic acids purification allowed isolation of DNA from purified Cryptosporidium parvum oocysts and ...
Dose-response studies of the radiosensitivity of spermatogonial stem cells in various epithelial stages after irradiation with graded doses of fission neutrons of 1 MeV mean energy were carried out in the Cpb-N mouse. These studies on the stem cell population in stages IX-XI yielded simple exponential lines characterized by an average D0 value of 0.76 +/- 0.02 Gy. In the subsequent epithelial stages XII-III, a significantly lower D0 value of 0.55 +/- 0.02 Gy was found. In contrast to the curves obtained for stem cells in stages IX-III, the curves obtained in stages IV-VIII indicated the presence of a mixture of radioresistant and radiosensitive stem cells. In stage VII, almost no radioresistant stem cells appeared to be present and a D0 value for the radiosensitive stem cells of 0.22 +/- 0.01 Gy was derived. Previously, data were obtained on the size of colonies (in number of spermatogonia) derived from surviving stem cells. Combining these data with data from the ...
In the bacterial reversion assay with S. typhimurium TA98, TA100, TA1535 and TA1537, gamma irradiated hyaluronic acid (10 and 50 kGy) did not induce a significant increase in the number of revertant colonies in the presence of S9 metabolic activation system. In chromosomal aberration tests with CHO cells, gamma irradiated hyaluronic acid (10 and 50 kGy) did not result in an increase in the frequency of chromosomal aberrations. In vivo mouse micronucleus assay, gamma irradiated hyaluronic acid (10 and 50 kGy) did not show an increase in the frequency of polychromatic erythrocytes with micronuclei. These results indicate that hyaluronic acids irradiated at 10 and 50 kGy did not show any genotoxic effects under these experimental conditions. In order to evaluate their possible subacute toxicity, the male and female of ICR mouse were given to methanol extract of 50 kGy irradiated red ginseng and 20 kGy irradiated water extract of mistletoe for ...
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 sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) #alpha#subunit forms a binding site for #alpha#-bungarotoxin (#alpha#-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR #alpha#1 subunits were tested for their ability to bind "1"2"5I-#alpha#-BTX, and differences in #alpha#-BTX affinity were determined by using solution (IC_5_0s) and solid-phase (K_ds) assays. Panels of overlapping peptides corresponding to the complete #alpha#1 subunit of mouse and human were also tested for #alpha#-BTX binding, but other sequence segments forming the #alpha#-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased #alpha#-BTX binding, whereas ...
Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which ...
A major regulatory element required for expression of the human [alpha]-globin genes is located 40 kb upstream of the embryonic [zeta]-globin gene. To understand how this and other locus control region (LCR) elements contribute to high-level expression in erythroid cells, we have performed high-resolution, in vivo dimethyl sulfate footprinting. In addition, we have modified the dimethyl sulfate-based ligation-mediated polymerase chain reaction in vivo footprinting procedure to permit the assessment of interactions at guanine and adenine residues, rather than guanines alone. In vivo footprinting of the human [alpha]-LCR element carried on chromosome 16 in a mouse erythroleukemia cell environment revealed protein occupancy at GATA-1, AP-1/NF-E2, and CACC/GGTGG motifs, specific differences compared with in vitro protein binding, and distinct changes in one region upon dimethyl sulfoxide-induced cellular maturation. No protein contacts were detected in nonexpressing ...
The detection and quantification of defined reaction products of chemical mutagens and carcinogens (and of many cancer chemotherapeutic agents) with DNA require highly sensitive analytical techniques. The exceptional capability of immunoglobulins to recognize subtle alterations of molecular structure (especially when monoclonal antibodies are used to maximize specificity), outstanding sensitivity of immunoanalysis by high-affinity antibodies, and the fact that radioactively-labelled agents are not required suggest the utility of a radioimmunoassay to recognize and quantitate alkylated DNA products. We have recently developed a set of high-affinity monoclonal antibodies (secreted by mouse x mouse as well as by rat x rat hybridomas; antibody affinity constants, 10"9 to > 10"1"0 lmol) specifically directed against several DNA alkylation products with possible relevance in relation to both mutagenesis and malignant transformation of mammalian ...
Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs adenosine 5'-(beta, gamma-imido)triphosphate ...
Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic ({alpha}-A1) and a distinct basic ({beta}-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of the human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human ...
Institutional and organizational models ... Review individual centre institutional and organizational models in the light of the tasks to be performed by
We study a variant of the Penner-Distler-Vafa model, proposed as a c = 1 quantum gravity: quenched' matrix model with logarithmic potential. The model is exactly soluble, and exhibits a two-cut branching as observed in multicritical unitary matrix models and multicut Hermitian matrix models. Using analytic continuation of the power in the conventional polynomial potential, we also show that both the Penner-Distler-Vafa model and our quenched' matrix model satisfy Virasoro algebra constraints.
The role of natural enemies in the regulation of populations is one of the major questions facing population ecologists. Simplification have led to two theoretical ways of incorporating the role of natural enemies in single ecological models: diffusion models and patch-type models. The predictions of the models are different because of the way variability is incorporated. Three equations are presented for diffusion models and one for patch models. Since the two types of models apply at different combinations of spatial and temporal scales, the right model(s) to choose for a particular study requires careful assessment. A continuing dialogue between experimentalists and theoreticians will lead to a better understanding of natural systems such as those that occur in biological control.
The presence of endothelin (ET)-like immunoreactivity and the cardiovascular effects of mammalian ET-1 in fish have been reported. To identify ET-related peptides in fish, we screened the cDNA library of the salmon (Oncorhynchus keta) stomach by means of rapid amplification of cDNA ends, and we cloned cDNAs encoding an ET-related peptide. The salmon ET-related sequence of 21 amino acids is identical to the trout ET-1 peptide recently purified from kidney specimens of Oncorhynchus mykiss. The deduced amino acid sequence of salmon pre-proET-1 (PPET-1) comprises 244 amino acids, including a putative signal sequence and mature ET-1, as well as big ET-1 and ET-1-like sequences. This precursor, the first reported PPET-1 sequence for Salmoniformes, Teleostei, has low homology with the sequences of human, mouse, frog (Xenopus laevis), and zebrafish (Danio rerio) PPET-1 (26%, 29%, 24%, and 39%, respectively). PMID:16740985
Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells. In the present study, we first cloned a rat PGC-1 gene from a brown adipose tissue cDNA library which encodes a predicted 796-amino-acid protein and exhibits respectively 98% and 95% identity with the mouse and human homologues. Next, we examined the effect of swimming exercise training on the level of expression of the PGC-1 gene in rat epitrochlearis (Epi) muscle. PGC-1 mRNA level in Epi muscle in rats that swam 2 h a day for 3 and 7 days increased dramatically by 154% and 163%, respectively, compared to the non-exercised control group. PGC-1 mRNA up-regulation was not observed in an immersion group treated at 35 degrees C during the training program but without swimming exercise. These results demonstrate that expression of the PGC-1 gene in Epi muscle is induced not only ...
Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after ...
The tissue distribution of "1"3"1I-transferrin ("1"3"1I-Tf) was studied in athymic nude mice having s.c. human colonic adenocarcinoma HT-29 xenografts. Four days after "1"3"1I-Tf injection, the "1"3"1I specific activity measured in the HT-29 tumor, i.e. amount of radioactivity per gram of fresh tissue, represented 0.31 #+-# 0.09% of the injected radioactivity and was 1.90 fold more than that measured in the murine colon (P < 0.05). After correction for intravascular "1"3"1I-Tf as estimated by mean of "9"9"mTc-Sn in vivo labeling of red blood cells, the "1"3"1I specific activity observed in the HT-29 tumor was 7.21 fold more than that observed in the murine colon. This subtracting method enabled us to localize a HT-29 tumor xenograft by #gamma# scintigraphy of the entire animal and demonstrated that "1"3"1I-Tf could be a non-specific but potent marker for human colon cancer. (author).
Understanding risks from exposures to carcinogens and other chemicals depends upon measurement of their dose to target tissues and their reactivity with critical macromolecules. The authors have used AMS detection of radio-isotopes to assess doses and reactivities at low, environmentally relevant doses. Several biomedical investigations show the effectiveness of quantification of biologically important events at extremely high sensitivity with AMS. Specifically, they have measured the addition of environmental carcinogens such as 2-amino-3,8-dimethylimidazo[4,5-f]-quinoaxaline (MelQx), a chemical found in cooked food, to DNA at concentrations relevant to human exposure. Other low level detection problems in biology, such as immunoassay assessment of small environmental chemicals, is being developed with attomole sensitivity. AMS also aids the assessment of genotoxic risks from chemicals by quantifying the binding of labeled chemicals to DNA. The very toxic and potent carcinogen, ...
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 activation. Our findings ...
The effect of adriamycin in combination with radiation on the skin reactions of mouse feet has been examined under a variety of experimental conditions including: (a) hyperthermic treatment of the foot immediately following adriamycin administration, with the former given either just before or just after x irradiation, and (b) fractionated treatments of drug and radiation in a variety of sequences over an 18-day period. In the case of the most severe hyperthermic treatment, no increased radiation reactions were observed in the presence of adriamycin. However, in the case of the less severe hyperthermic treatment a small but significant increase in skin reactions was observed. In the study of fractionated drug and radiation treatments, an enhancement of reaction in those animals receiving combined modality treatment over those receiving radiation alone was seen in those groups where the initiation of drug treatment succeeded the initiation of radiation treatment by ...
Abstract in english The tegument surface of the adult schistosome, bounded by a normal plasma membrane overlain by a secreted membranocalyx, holds the key to understanding how schistosomes evade host immune responses. Recent advances in mass spectrometry (MS), and the sequencing of the Schistosoma mansoni transcriptome/genome, have facilitated schistosome proteomics. We detached the tegument from the worm body and enriched its surface membranes by differential extraction, before subjecting t (more) he preparation to liquid chromatography-based proteomics to identify its constituents. The most exposed proteins on live worms were labelled with impearmeant biotinylation reagents, and we also developed methods to isolate the membranocalyx for analysis. We identified transporters for sugars, amino acids, inorganic ions and water, which confirm the importance of the tegument plasma membrane in nutrient acquisition and solute balance. Enzymes, including phosphohydrolases, esterases and ...
Ultra-high resolution radiographs can be obtained using synchrotron X-rays. A collaboration team consisting of K-JIST, POSTECH and YUMC has recently commissioned a new beamline (5C1) at Pohang Light Source (PLS) in Korea for medical applications using phase contrast radiology. Relatively simple image acquisition systems were set up on 5C1 beamline, and imaging studies were performed for resolution test patterns, mammographic phantom, and animals. Resolution test patterns and mammographic phantom images showed much better image resolution and quality with the 5C1 imaging system than the mammography system. Both fish and mouse images with 5C1 imaging system also showed much better image resolution with great details of organs and anatomy compared to those obtained with a conventional mammography system. A simple and inexpensive ultra-high resolution imaging system on 5C1 beamline was successfully implemented. The authors were able to acquire ultra-high resolution ...
The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has nor been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins.More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide ...
Micropatterned materials were obtained by a controlled laser ablation of a photoimmobilised homogeneous layer of hyaluronic acid (Hyal) and its sulphated derivative (HyalS). The photoimmobilisation was performed by coating the polysaccharide, adequately functionalised with a photoreactive group, on aminosilanised glass substrate and immobilising it on the surface under UV light. Hyal or HyalS photoimmobilised samples were then subjected to laser ablation with wavelengths in the UV regions in order to drill the pattern. Four different patterns with stripes of 100, 50, 25 and 10 {mu}m were generated. A chemical characterisation by attenuated total reflection/Fourier transform infrared (ATR/FT-IR) and time of flight-secondary ions mass spectrometry (TOF-SIMS) confirmed the success of the laser ablation procedure and the presence of alternating stripes of polysaccharide and native glass. The exact dimensions of the stripes were determined by atomic force microscopy. The analysis of cell ...
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 physiological process(es) which establishes a large ...
Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study demonstrated a dose-response effect on length of mitotic delay and, ...
Glycosaminoglycan synthesis by two subpopulations of a mouse mammary tumor cell line was compared. The two sublines express distinctly different growth characteristics in vitro and in vivo which indicate differences in growth regulation. Newly made glycosaminoglycans were recovered from the culture media, the cell surfaces, and residual cellular material. The cell population which grows more aggressively in vivo (+SA subline, a subline that grows in soft agarose) incorporated about 8 times more (/sup 14/C)glucosamine per cell into total glycosaminoglycans than did the slower-growing population (-SA subline, which does not grow in soft agarose). Appropriate control experiments indicated that the apparent difference in rates of synthesis was not due to discrepancies in glucosamine uptake. The main residual cellular molecule labeled was heparan sulfate, but the predominant molecule at the cell surface and in the culture fluid was hyaluronic acid. Overall, +SA cells ...
This study was carried out to evaluate the biochemical and morphological effects of ionizing radiation on ovary. Immature mice (ICR, 3 week-old) were irradiated at a dose of LD{sub 80(30)} at KAERI. The ovaries were collected after 6 hours, 12 hours, 1 day, and 2 days post irradiation. To analyze the morphological changes, histological staining with hematoxylin-eosin, immuno- histochemical preparation using in situ 3'-end labeling was performed. DNA fragmentation analysis and flowcytometric evaluation of DNA extracted from whole ovary were performed. As a result of DNA fragmentation analysis, DNA fragments with 185, 370, and 555 base pairs were clearly shown at 6 hours post irradiation. The percentage of A{sub 0} cell cycle was significantly increased in the irradiated group than control. In situ 3'-end labeled follicles were increased at 6 hours post irradiation. The radiation-induced follicular atresia was taken place via an apoptotic degeneration. And this ...
Abnormal intracellular deposition of aggregated ?-synuclein is the characteristic feature of a number of neurological disorders, including Parkinson's disease (PD). Although ?-synuclein is typically known as a cytosolic protein, a small amount is secreted by exocytosis in both monomeric and aggregated forms. The extracellular forms of ?-synuclein in human body fluids, such as cerebrospinal fluid (CSF) and blood plasma, might be a diagnostic target for PD and related diseases. Here, we characterized a new set of monoclonal antibodies against ?-synuclein, and using different combinations of antibodies, we established ELISA systems to specifically detect human ?-synuclein, mouse and human ?-synuclein together, and multimeric forms of ?-synuclein in biological samples. By employing the Tyramide signal amplification method, the sensitivity of the assay was significantly improved to detect a concentration as low as ?12.5 pg/ml. These assays might be useful tools for ...
Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10/sup 7/ cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10/sup 6/ re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10/sup 7/ cells per flask. Based on these results, a possibility that a stimulator of stem cell proliferation, released from irradiated stromal cells, is cancelled by an inhibitory factor produced by irradiated or unirradiated haemopoietic cells is postulated.
Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10/sup -7/ to 10/sup -2/ M. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 ..mu..M. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidation which would be expected if lipid peroxidation had occurred in vivo although extensive lung damage developed during this time period. These results indicate that paraquat does not cause pulmonary toxicity by ...
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 ...
Bone morphogenetic protein (BMP)-4 has a crucial role on primordial germ cells (PGCs) development in vivo which can promote stem cell differentiation to PG-like cells. In this study, we investigated the expression of Mvh as one of the specific genes in primordial germ cells after treatment with different doses of BMP4 on bone mesenchymal stem cells (BMSCs)-derived PGCs. Following isolation of BMSCs from male mouse femur and tibia, cells were cultured in medium for 72?h. Passage 4 murine BMSCs were characterized by CD90, CD105, CD34, and CD45 markers and osteo-adipogenic differentiation. Different doses of BMP4 (0, 0.01, 0.1, 1, 5, 25, 50, and 100?ng/ml) were added to BMSCs for PGCs differentiation during 4-days culture. Viability percent, proliferation rates, and expression of Mvh gene wer...
Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage {lambda} was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a {lambda}gt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the gene was mapped to chromosome 17q21-22 by in situ hybridization of a cloned fragment to metaphase chromosomes ...
The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, each of these receptors in human and mouse ...
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 prolongation was apparent for about five days and thereafter growth caught up. These results suggest that neonatal asphyxia has ...
Aim/hypothesis We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. Methods Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55?mg/kg), diabetic + aliskiren (10?mg?kg?1?day?1, pump), or diabetic + lisinopril (10?mg?kg?1?day?1, drinking water) rats were evaluated over 16?weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22?h/day) from postnatal days?0 to 11, and then room air from postnatal days?12 to 18. Aliskiren (10 or 30?mg?kg?1?day?1, pump) or lisinopril (10?mg...
A technique for delivering genes carried by recombinant retroviruses into specific cell types could have numerous applications in oncology, developmental biology, and gene therapy. As a first step toward this remote goal the authors designed a procedure allowing in vitro cell targeting by retroviruses. Biotinylated antibodies against the viral envelope protein on one side, and against specific cell membrane markers on the other side, were bridged by streptavidin and used to link the virus to the host. The method was successfully used to infect human cells with ecotropic murine retroviruses by means of major histocompatibility complex class I and class II antigens and appears easily adaptable to other cell, membrane markers. Moreover, the sequential protocol they design, although allowing infection of human cells, requires less stringent safety constraints than would handling of amphotropic virus stocks.
Computers have a direct impact on our lives nowadays. Human's interaction with the computer has modified with the passage of time as improvement in technology occurred the better the human computer interaction became. Today we are facilitated by the operating system that has reduced all the complexity of hardware and we undergo our computation in a very convenient way irrespective of the process occurring at the hardware level. Though the human computer interaction has improved but it's not done yet. If we come to the future the computer's role in our lives would be a lot more rather our life would be of the artificial intelligence. In our future the biggest resource would be component of time and wasting time for a key board entry or a mouse input would be unbearable so the need would be of the computer interaction environment that along with the complexity reduction also minimizes the time wastage in the human computer interaction. Accordingly in our future the ...
Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...
A previously studied theory of gravitation in flat space-time is applied to homogeneous and isotropic cosmological models. There exist two different classes of models without singularities: (i) ever-expanding models, (ii) oscillating models. The first class contains models with hot big bang. For these models there exist at the beginning of the universe-in contrast to Einstein's theory-very high but finite densities of matter and radiation with a big bang of very short duration. After short time these models pass into the homogeneous and isotropic models of Einstein's theory with spatial curvature equal to zero and cosmological constant ALPHA >= O.
terms of 11) numerical models, 2D SPH simulations, and analytic models. The 1D model was useful for determining the evolution over very long timescales. ...
Models can be useful at many different levels when considering complex issues such as biological control of mosquitoes. At an early stage, exploratory models are valuable in exploring the characteristics...Full Text Available
A new supersymmetric gauge-invariant model is proposed. It is shown that the hidden-symmetry algebra for this model is the Kac-Moody algebra without a center.
Engine model: An engine and governor model adapted from a heavy lift helicopter simulation provides a restistic time delay between aerodynamic rotor ...
The Inner Model Hypothesis (IMH) and the Strong Inner Model Hypothesis (SIMH) were introduced by the first author in ``Internal consistency and the inner model hypothesis'', Bulletin of Symbolic Logic, December 2006. In this article we establish some upper and lower bounds for their consistency strength.
This 1978 annual report contains the results of ''Seismic testing of Wolsung-1 steam generator model'' which was initiated in 1977 as a part of a study on nuclear components testing. Model 78, improved version of Model 77 which did not take into account f...
Cardiovascular modelling has been a major research subject for the last decades. Different cardiac models have been developed at a cellular level as well as at the whole organ level. Most of...Full Text Available
... trees, data showing a better fit to a power model than to a negative exponential model. Invading Pinus ... power law models were significantly negative. The inverse power model accounted for a considerabl...
In recent years the modelling of interannual climate variability has been studied, the atmospheric energy and water cycles, and climate simulations with the ECHAM3 model. In addition, the climate simulations of several models have been compared with special emphasis in the area of northern Europe
processes, we construct a stochastic dynamic model for air- craft counts in ... Also , queueing models for the arrival of aircraft at ... A queueing model has also been used to study ...... Assignment and Aircraft-Sequencing Algorithms in Terminal ...
This paper presents research work concerning the mathematical modelling of air pollution in the Athens basin. A mathematical model based on aerodynamics and conservation equations together with turbulence modelling in body-fitted coordinates is used to provide the necessary input information to a similar but more detailed (i.e. small scale) model around Athens. Both models consist of solving the full Navier-Stokes equations and take into account the precise topography of the region. Different roughness heights are used for sea, coastal regions and land. The smaller scale model makes use of a two-equation turbulence model ({kappa}-{epsilon}) and the large scale model assumes a constant turbulence viscosity. The pollutant sources used in these models are based on actual emissions in the Athens area and ...
... a way to model a munition's terminal effects in a ... following attributes are handled in a stochastic fashion ... be improved by managing a queue of buffers ...
... They comprise of a power model for the representation of the electric system, a fluid model that represents the cooling fluid flow, three layers of ...
Non-linear autoregressive Markov regime-switching models are intuitive. Time-series approaches for the modelling of electricity spot prices are frequently proposed. In this paper, such models are compared with an ordinary linear autoregressive model with regard to their forecast performances. The study is carried out using German daily spot-prices from the European Energy Exchange in Leipzig. Four non-linear models are used for the forecast study. The results of the study suggest that Markov regime-switching models provide better forecasts than linear models. (author)
Non-linear autoregressive Markov regime-switching models are intuitive. Time-series approaches for the modelling of electricity spot prices are frequently proposed. In this paper, such models are compared with an ordinary linear autoregressive model with regard to their forecast performances. The study is carried out using German daily spot-prices from the European Energy Exchange in Leipzig. Four non-linear models are used for the forecast study. The results of the study suggest that Markov regime-switching models provide better forecasts than linear models. (author)
Decision-making is strongly based on modelling in two of our water supply projects concerning artificial ground water. The model used is a 2-dimensional flow and transport model using the element method. Due to sharp variations in Finnish soils, the modelling process is based on careful and detailed evaluation of basic hydrogeological data before and during model calibration.
The concept of frailty offers a convenient way to introduce unobserved heterogeneity and associations into models for survival data. In its simplest form, frailty is an unobserved random proportionality factor that modifies the hazard function of an individual or a group of related individuals. "Frailty Models in Survival Analysis" presents a comprehensive overview of the fundamental approaches in the area of frailty models. The book extensively explores how univariate frailty models can represent unobserved heterogeneity. It also emphasizes correlated frailty models as extensions of
Using the operator approach we reexamine the two-dimensional model describing a massive Fermi field interacting via derivative couplings with two massless Bose fields, one scalar and the other pseudoscalar. Performing a canonical transformation on the Bose field algebra, the Fermi field operator is written in terms of the Mandelstam soliton operator and the derivative-coupling (DC) model is mapped into the massive Thirring model with two vector-current-scalar-derivative interactions (Schroer-Thirring model). The DC model with massless fermions can be mapped into the massless Rothe-Stamatescu model with a Thirring interaction (massless Rothe-Stamatescu-Thirring model). Within the present approach the weak equivalence between the fermionic sector of the DC model and the massive Thirring model is ...
This paper proposes the use of particle swarm optimization method (PSO) for finite element (FE) model updating. The PSO method is compared to the existing methods that use simulated annealing (SA) or genetic algorithms (GA) for FE model for model updating. The proposed method is tested on an unsymmetrical H-shaped structure. It is observed that the proposed method gives updated natural frequencies the most accurate and followed by those given by an updated model that was obtained using the GA and a full FE model. It is also observed that the proposed method gives updated mode shapes that are best correlated to the measured ones, followed by those given by an updated model that was obtained using the SA and a full FE model. Furthermore, it is observed that the PSO achieves this accuracy at a computational speed that is faster than that by the ...
A constitutive model for an explosive consists of three parts: equation of state of reactants, equation of state of products, and reaction rate. In the absence of a good physical theory, models are empirical and based on heuristics. For the HMX based plastic-bonded explosive PBX 9501, three models have previously been calibrated and used in numerical simulations. Here, these three models are compared. They illustrate several generic difficulties with developing and validating models. The available data is insufficient to determine a constitutive model uniquely. Different models can be calibrated to fit the available data yet differ significantly in regions of phase space of importance to applications. Comparing models gives an indication of the uncertainty in model predictions outside the ...
A detailed component-based simulation model of a geothermal heat pump system has been calibrated to monitored data taken from a family housing unit located at Fort Polk, Louisiana. The simulation model represents the housing unit, geothermal heat pump, ground heat exchanger, thermostat, blower, and ground-loop pump. Each of these component models was tuned to better match the measured data from the site. These tuned models were then interconnected to form the system model. The system model was then exercised in order to demonstrate its capabilities.
A detailed component-based simulation model of a geothermal heat pump system has been calibrated to monitored data taken from a family housing unit located at Fort Polk, Louisiana. The simulation model represents the housing unit, geothermal heat pump, ground heat exchanger, thermostat, blower, and ground-loop pump. Each of these component models was 'tuned' to better match the measured data from the site. These tuned models were then interconnect to form the system model. The system model was then exercised in order to demonatrate its capabilities.
This paper introduces a new way of estimating parameters in a Brownian motion regime switching asset model to incorporate volatility clustering. The regime switching model is then applied to pricing of up-and-in barrier call options. We take the probability of crossing the barrier between simulation points into account, and we increase accuracy in simulations by importance sampling. The regime switching model is compared to the Normal Inverse Gaussian model and the traditional Black-Scholes model, and option prices from the regime switching model are compared to the closed form expression of up-and-in barrier calls in a Black-Scholes market.
The National Energy Modeling System (NEMS) developed by the U.S. Department of Energy`s Energy Information Administration is a well-recognized model that is used to project the potential impact of new electric generation technologies. The NEMS model does not presently have the capability to model energy storage on the national grid. The scope of this study was to assess the feasibility of, and make recommendations for, the modeling of battery energy storage systems in the Electricity Market of the NEMS. Incorporating storage within the NEMS will allow the national benefits of storage technologies to be evaluated.
An integrated approach to the modelling of hydrogen assisted failure in 316L steel is presented. The approach includes experimental, fractographic, numerical and theoretical analysis of the phenomenon. The physical adequacy of the mechanical models of hydrogen embrittlement (notch extension model and notch cracking model) is discussed by comparing the virtual damage depth (theoretical) predicted by the models with the embrittled zone (microphysical) measured in the fractographic analysis by scanning electron microscopy. In addition, a numerical modelling of hydrogen diffusion is performed, concluding that bulk diffusion is not important in hydrogen embrittlement of 316L steel, so that hydrogen transport accelerated by the microdamage itself should be taken into account. (orig.)
The constitutive model used to describe the deformation of crushed salt is presented in this report. Two mechanisms -- dislocation creep and grain boundary diffusional pressure solution -- are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. Upon complete consolidation, the crushed-salt model reproduces the Multimechanism Deformation (M-D) model typically used for the Waste Isolation Pilot Plant (WIPP) host geological formation salt. New shear consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on WIPP and southeastern New Mexico salt. Nonlinear least-squares model fitting to the database produced two sets of material parameter values for the ...
The SMART (System-integrated Modular Advanced ReacTor) which is a 330 MWt advanced integral PWR was developed by the KAERI (Korea Atomic Energy Institute) for electricity generation and seawater desalination. A thermal hydraulic evaluation and analysis of the SMART is performed by the TASS /SMR-S (Transient And Setpoint Simulation/System integrated Modular Reactor-Safety). The TASS/SMR-S code has various models reflecting the design features of the SMART such as the drift flux model, the core models (core power and core heat transfer model), the component models, and the specific models. One of the core models is the core heat transfer model. The role of this model is to calculate the heat flux and radial temperature profiles at a fuel rod surface using the relevant heat transfer correlations for all ...
The objective of this Task Group is the coordination of research studies on biokinetic models and the evaluation of the implications of new biokinetic models on dose assessment and safety standards. For this the new ICRP models, which will be used for a revision of ICRP Publications 30, 54, 68 and 78, are implemented into six different computer codes in five European countries and quality assured by intercomparison procedures. The work has started with the implementation of the new ICRP Alimentary Tract Model. New systemic models and the new NCRP wound model will follow. The work also includes the evaluation of experimental results in terms of formulation by the new model structures and a quality assurance of model formulation. PMID:17556343
A class of nonlinear models combining a pharmacokinetic compartmental model and a pharmacodynamic Emax model is introduced. The locally D-optimal (LD) design for a four-parameter composed model is found to be a saturated four-point uniform LD design with the two boundary points of the design space in the LD design support. For a five-parameter composed model, a sufficient condition for the LD design to require the minimum number of sampling time points is derived. Robust LD designs are also investigated for both models. It is found that an LD design with $k$ parameters is equivalent to an LD design with $k-1$ parameters if the linear parameter in the two composed models is a nuisance parameter. Assorted examples of LD designs are presented.
The heat capacity and heat of fusion were measured for a number of minerals using differential scanning calorimetry (DSC). The DSC measurements showed that the heat of fusion for the minerals is very low compared to the heat of fusion for pure crystalline phases reported elsewhere. A model for the melting behaviour of mineral materials in terms of melting interval, heat capacities and heat of fusion has been developed. The only model input is the chemical composition of the mineral material. The model was developed to be implemented in a detailed model of a cupola furnace, thus the focus for the development was not only precision but also to obtain a model that was continuous and differentiable. The model is based on several different submodels that each covers a part of the heating and melting of rocks. Each submodel is based on large amounts of empirical data. ...
Stylized numerical models of the tooth are usually employed in qualification procedure related to Electronic Paramagnetic Resonance in long-term accidental contamination dose reconstruction. In this work a voxel model was developed from the microCT image data set of a human non contaminated molar tooth. A stylized model, reproducing the characteristics of the voxel model, was also created in order to investigate the level of accuracy that can be obtained in this kind of study.
The high-power model of Disk-and Washer (DAW) cavity for electron acceleration is under fabrication. Basic Dimensions of the cavity were determined from aluminum model measurement and electromagnetic field calculation. We have fabricated model made of OFC (Oxygen Free Copper) five times in total. Some details are optimized and corrected, and then the final brazing are proceeding. These model results and present status are described. (author)
This document generates a supernatant hydroxide ion depletion model based on mechanistic principles. The carbon dioxide absorption mechanistic model is developed in this report. The report also benchmarks the model against historical tank supernatant hydroxide data and vapor space carbon dioxide data. A comparison of the newly generated mechanistic model with previously applied empirical hydroxide depletion equations is also performed.
This report to the Nuclear Regulatory Commission (NRC) describes the development and application of a methodology to systematically and quantitatively assess predictive uncertainty in groundwater flow and transport modeling that considers the combined impact of hydrogeologic uncertainties associated with the conceptual-mathematical basis of a model, model parameters, and the scenario to which the model is applied. The methodology is based on a n extension of a Maximum Likelihood implementation of Bayesian Model Averaging. Model uncertainty is represented by postulating a discrete set of alternative conceptual models for a site with associated prior model probabilities that reflect a belief about the relative plausibility of each model based on its apparent consistency with available knowledge and ...
In this paper we present a modeling framework for analyzing computer models with two types of variations. The paper is based on a case study of an orthopedic surgical unit, which has both controllable and uncontrollable factors. Our results show that this structure of variation can be modeled effectively with linear mixed effects models and generalized additive models. Copyright (C) 2009 John Wiley & Sons, Ltd.
This paper presents a case study in the design and implementation of a numerical weather prediction model on a supercomputer (CRAY-1). Following a historical introduction to the evolution of the model, the governing equations of the model are presented and the numerical solution of these forecast equations is described. A brief tutorial on the architecture of the CRAY-1 is presented with a discussion of how it affects the choice of algorithms and code design of the model. A summary of the advantages gained by use of the vector aspects of the CRAY-1 is included.
Tree-level scattering amplitudes of longitudinally polarized electroweak vector bosons in the Standard Model are calculated using Mathematica package Feyncalc. The modifications of low-energy theorems for longitudinally polarized W and Z in the Standard Model are discussed.
The brain maintains internal models of its environment to interpret sensory inputs and prepare actions. While behavioral studies demonstrated that these internal models are optimally adapted...Full Text Available
We obtain a symmetry algebra for any unitary minimal model by using the representation of conformal field theories. This symmetry algebra can be interpreted as a quantum group. The generalization to non-unitary minimal models is direct. (orig.).
We obtain a symmetry algebra for any unitary minimal model by using the representation of conformal field theories. This symmetry algebra can be interpreted as a quantum group. The generalization to non-unitary minimal models is direct. (orig.).
BackgroundLiquid chromatography-mass spectrometry (LC-MS) is one of the major techniques for the quantification of metabolites in complex biological samples. Peak modeling is one...Full Text Available
SummaryWe develop a new class of models, dynamic conditionally linear mixed models, for longitudinal data by decomposing the within-subject covariance matrix using a special Cholesky...Full Text Available
In this paper two different models of brain regulation of exercise performance are critically compared: the central governor model proposed by Noakes and colleagues, and an alternative psycholobiological model based on motivational intensity theory. PMID:18618133
The report provides and overview of calculation models for the simulation of airflows and deals comprehensively with field and multi-zone models as well as the coupling of individual zone and multi-zone models. Examples of calculations are given. figs., tabs., refs.
We show the existence of a rather general class of closed cosmological models of Bianchi type IX that do not exhibit recollapse but expand for all times. This is despite the fact that these models satisfy the strong energy condition by a wide margin.
A new 3D model is developed to simulate the self-oscillation of the elongated vocal folds. This model allows for large deformation and longitudinal displacement. The displacement boundary condition...Full Text Available
We present the formulation and testing of a mathematical model for the kinetics of homotypic cellular aggregation. The model considers cellular aggregation under no-flow conditions as a two-step process....Full Text Available
New habitat-based models for spread of hantavirus are developed which account for interspecies interaction. Existing habitat-based models do not consider interspecies pathogen transmission,...Full Text Available
Volume VII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the tritium transport model documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.
Volume VI of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the groundwater flow model data. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.
;Contents: Comparison of Simulation Modules of TRANSYT and INTEGRATION Models; Evaluation of SCATSIM-RTA Adaptive Traffic Network Simulation Model; Comparison NETSIM, NETFLO I, and NETFLO II Traffic Simulation Models for Fixed-Time Signal Control; Traffic Flow Simulation Through Parallel Processing; Cluster Analysis as Tool in Traffic Engineering; Traffic Platoon Dispersion Modeling on Arterial Streets; Hybrid Model for Estimating Permitted Left-Turn Saturations Flow Rate; and Passing Sight Distance and Overtaking Dilemma on Two-Lane Roads.
Geochemical model is a kind of concept model which describes geochemical processes by means of chemical reaction equations and mathematical formula, and the software based on the concept model are called geochemical modeling code. Geochemical modeling codes can be divided into three categories: mass equilibrium, mass transfer and mass transport code. The major functions of geochemical codes include the calculation of forms of occurrence of elements, the prediction of direction of various geochemical reaction, the dissolution and precipitation of elements, the pH and Eh value, the rate and path of geochemical reaction in aqueous solution.
We discuss the asymptotic dynamical evolution of spatially homogeneous brane-world cosmological models close to the initial singularity. We find that generically the cosmological singularity is isotropic in Bianchi type IX brane-world models and consequently these models do not exhibit Mixmaster or chaotic-like behaviour close to the initial singularity. We argue that this is typical of more general cosmological models in the brane-world scenario. In particular, we show that an isotropic singularity is a past-attractor in all orthogonal Bianchi models and is a local past-attractor in a class of inhomogeneous brane-world models. (letter to the editor)
In this letter, they present the results on a global fit to precision electroweak data in a Higgs triplet model. In models with a triplet Higgs boson, a consistent renormalization scheme differs from that of the Standard Model and the global fit shows that a light Higgs boson with mass of 100-200 GeV is preferred. Triplet Higgs bosons arise in many extensions of the Standard Model, including the left-right model and the Little Higgs models. The result demonstrates the importance of the scalar loops when there is a large mass splitting between the heavy scalars. It also indicates the significance of the global fit.
In this paper extended models for estimating price developments on electricity markets are presented. The models consider deviations from the normality hypothesis of the prices. Based on an ARMA model combination with GARCH, Gaussian-mixture and switching-regime approaches are comparatively discussed. The comparison is based on historic electricity prices of the spot and two reserve markets in Germany. It is shown that the proposed extended models lead to significantly improved representations of the considered stochastic price processes. It is inferred that these models may be preferred for estimating price developments on electricity markets. (author)