BackgroundTo investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).MethodsThe Aurora B and Aurora...Full Text Available
Poplar (Populus tremula × alba) lignins with exceedingly high syringyl monomer levels are produced by overexpression of the ferulate 5-hydroxylase (F5H) gene...Full Text Available
BackgroundMultidrug resistance (MDR) is a major obstacle in cancer treatment and is often the result of overexpression of the drug efflux protein, P-glycoprotein (P-gp), as a consequence...Full Text Available
Metabolic engineering of photosynthetic organisms is required for utilization of light energy and for reducing carbon emissions.Control of transcriptional regulators is a powerful approach for changing cellular dynamics, because a set of genes is concomitantly regulated. Here, we show that overexpression of a group 2 ? factor, SigE, enhances the expressions of sugar catabolic genes in the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Transcriptome analysis revealed that genes for the oxidative pentose phosphate pathway and glycogen catabolism are induced by overproduction of SigE. Immunoblotting showed that protein levels of sugar catabolic enzymes, such as glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glycogen phosphorylase, and isoamylase, are increased. Glycogen levels are reduced in the SigE-overexpressing strain grown under light. Metabolome analysis revealed that metabolite levels of the TCA cycle and ...
Background:The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who...Full Text Available
AbstractThis cohort study of 1302 persons aged ≥65 years, conducted in the Yoruba-speaking regions of Nigeria, determines the prevalence and correlates of hearing impairment (HI)...Full Text Available
BackgroundCognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors...Full Text Available
ObjectivesMild Cognitive Impairment (MCI) case-finding criteria have low specificity in general population studies. The present study retrospectively identifies cases...Full Text Available
AimTo estimate the prevalence and causes of blindness and visual impairment in the population aged 40 years and over in Muyuka, a rural district in the South West Province...Full Text Available
Dyslexia (or reading disability) and specific language impairment (or SLI) are common childhood disorders that show considerable co-morbidity and diagnostic overlaps and have been suggested to share...Full Text Available
Chromosomal common fragile sites (CFSs) are genetically unstable regions of the genome that are induced by conditions that impair DNA replication. In this report, we show that treatment with the DNA...Full Text Available
The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml...Full Text Available
AimsTo evaluate the effects of gender, age, diabetes mellitus, renal and hepatic impairment on tadalafil pharmacokinetics and tolerability.MethodsSix...Full Text Available
For the evaluation of the kidney impairment, serum creatinine concentrations or glomerular filtration rates are mainly used, and the conditions of solitary or transplanted kidney and chronic dialysis...Full Text Available
Molecular Misreading (MM) is the inaccurate conversion of genomic information into aberrant proteins. For example, when RNA polymerase II transcribes a GAGAG motif it synthesizes at low frequency RNA...Full Text Available
BackgroundAKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of...Full Text Available
SUMMARYThe biologic and clinical significance of KIT overexpression that associates with KIT gain-of- function mutations occurring in subsets...Full Text Available
Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase...Full Text Available
BackgroundIn Saccharomyces cerevisiae galactose is initially metabolized through the Leloir pathway after which glucose 6-phosphate enters glycolysis. Galactose...Full Text Available
BackgroundThe expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations...Full Text Available
In order to efficiently utilize natural cellulose materials to produce ethylene, three expression vectors containing the ethylene-forming enzyme (efe) gene from Pseudomonas...Full Text Available
Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null ...Full Text Available
Microglia provide immune surveillance for the brain through both the removal of cellular debris and protection against infection by microorganisms and “foreign” molecules. Upon...Full Text Available
Mitochondrial heat shock protein 70 (mtHSP70) is found to play a primary role in cellular defense against physiological stress like exposure to environmental contaminants and helpful in the maintenance...Full Text Available
Muscular dystrophies (MDs) comprise a group of degenerative muscle disorders characterized by progressive muscle wasting and often premature death. The primary defect common to most MDs involves disruption...Full Text Available
Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella...Full Text Available
Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available
Background:The cardiac sodium–calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Since heart failure...Full Text Available
Small RAC/ROP-family G proteins regulate development and stress responses in plants. Transient overexpression and RNA interference experiments suggested that the barley (Hordeum vulgare)...Full Text Available
Growing evidences indicate that proteases are implicated in adipogenesis and in the onset of obesity. We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white...Full Text Available
Medulloblastoma and neuroblastoma belong to a group of neoplasms designated as primitive neuroectodermal tumors (PNETs). Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matrix-associated...Full Text Available
Amyloid precursor protein (APP), implicated in Alzheimer's disease, is a transmembrane protein of undetermined function. APP is cleaved by gamma-secretase that releases the APP intracellular domain...Full Text Available
IntroductionVarious multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing...Full Text Available
A pentapeptide open reading frame equipped with a canonical ribosome-binding site is present in the Escherichia coli 23S rRNA. Overexpression of 23S rRNA fragments containing the mini-gene renders cells...Full Text Available
We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)
Interaction of drilling fluids with a geothermal reservoir formation can result in significant permeability impairment and therefore reduced well productivity. This interaction is studied under simulated in situ geothermal conditions of overburden stress, pore fluid pressure, temperature, and pore fluid chemistry. Permeability impairment of an East Mesa KGRA reservoir material is evaluated as a function of stagnation time, drilling fluid, and temperature. Results indicate that all of these parameters contribute significantly to the magnitude and the reversibility of the impairment.
PURPOSE: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment thus requiring innovative and effective targeted therapies. The oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.EXPERIMENTAL DESIGN: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual Fluorescence in situ hybridization was performed to detect loss of heterozygosity at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in vivo tumorigenesis and ...
Dehydrins, a subfamily of group 2 LEA proteins, are intrinsically unstructured plant proteins that accumulate in the late stages of seed development and in vegetative tissues subjected to water deficit, salinity, low temperature, or abscisic acid treatment. In this study, we isolated and characterized ZmDHN2b, a maize dehydrin gene. The genomic organization of the ZmDHN2b gene and its expression in maize seedlings were analyzed. To investigate the function of ZmDHN2b, we generated transgenic tobacco plants constitutively overexpressing ZmDHN2b. Ectopic expression of ZmDHN2b in tobacco accelerated seed germination and seedling growth at 15?C. Furthermore, ZmDHN2b-overexpressing lines had lower levels of cold-induced malondialdehyde and less electrolyte leakage than wild-type tobacco at 4?C....
After fluid resuscitation, vasoactive drug treatment represents the major cornerstone for correcting any major impairment of the circulation. However, debate still rages as to the choice of agent, dose,...Full Text Available
Standard pancreatic resections, such as pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy, result in an important loss of normal pancreatic parenchyma and may cause impairment...Full Text Available
The identification of individuals at risk for Alzheimer's disease (AD) is essential for the timely administration of treatment approaches aimed at slowing the onset or progression of the disease....Full Text Available
Nutcracker phenomenon refers to compression of the left renal vein, most commonly between the aorta and the superior mesenteric artery, with impaired blood outflow often accompanied by distention...Full Text Available
Cerebral periventricular white matter injury stands as a leading cause of cognitive, behavioral and motor impairment in preterm infants. There is epidemiological and histopathological evidence...Full Text Available
BackgroundAlterations in protein composition and oxidative damage of high-density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of...Full Text Available
BackgroundPerfluoroalkyl acids (PFAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in...Full Text Available
Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood....Full Text Available
SynopsisAttention-deficit / hyperactivity disorder (ADHD) is a valid and impairing psychological disorder that persists into adulthood in a majority of cases and is associated...Full Text Available
Copper deficiency is associated with impaired brain development and mitochondrial dysfunction. Perinatal copper deficiency was produced in Holtzman rats. In vivo proton NMR...Full Text Available
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which...Full Text Available
BackgroundObsessive-compulsive disorder is associated with a relevant impairment in social and interpersonal functioning and severe disability. This seems to be particularly true...Full Text Available
Raeder described five patients with mixed features of trigeminal nerve pathology and oculosympathetic impairment, with or without other cranial nerve lesions. This constellation of clinical features...Full Text Available
High-level expression of mitotic arrest defective protein 2 (MAD2), a central component of the spindle assembly checkpoint, has been observed in a variety of human malignancies. Aim of the present study was to observe the expression of MAD2 in human non-small-cell lung cancer (NSCLC) and explore its clinicopathologic significance and evaluate MAD2 expression as a prognostic marker. MAD2 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 358 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level MAD2 expression was observed in 26.3% (94 of 358 cases), and correlated with male sex (P=0.0002), tumor progression (pT status) (P=0.0009), visceral or parietal pleural invasion (P=0.0151), non-adenocarcinoma, ...
An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.
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...
BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...
Identity is a part of self-consciousness, which is also expressed as ''being in the world'' which one in turn shows to others as the Self. The assessment of the Self in a population of patients with Alzheimer's disease, according to a multidimensional definition (physical, social, spiritual), showed that the social self was impaired, and the severity of impairment of the self was correlated to apathy and lack of semantic autobiographical memory. It also appears that ipseity is selectively affected by the disease.
Engineered overexpression of protein kinase Cα (PKCα) was previously shown to endow nonmotile MCF-10A human breast cells with aggressive motility. A traceable mutant of PKCα...Full Text Available
BackgroundAmplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within...Full Text Available
Unequal segregation of cell fate determinants at mitosis is a conserved mechanism whereby cell fate diversity can be generated during development. In Drosophila, each sensory organ...Full Text Available
The effect of the non-selective, 1-aminoindan-1,5-dicarboxylic acid (AIDA), and selective (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4- methoxycyclohexyl) methanone (JNJ16259685),...Full Text Available
Rice, the world's major staple crop, is a poor source of essential micronutrients, including folates (vitamin B9). We report folate biofortification of rice seeds achieved by overexpressing two Arabidopsis thaliana genes of the pterin and para-aminobenzoate branches of the folate biosynthetic pathway from a single locus. We obtained a maximal enhancement as high as 100 times above wild type, with 100 g of polished raw grains containing up to four times the adult daily folate requirement.
Nucleotide sequence analysis of the Escherichia coli chromosomal DNA inserted in the plasmid pLC33-5 of the Clarke and Carbon library [Clarke & Carbon (1976) Cell 9, 91-99] revealed the existence...Full Text Available
In vertebrates, the positioning of the internal organs relative to the midline is asymmetric and evolutionarily conserved. A number of molecules have been shown to play critical roles in left-right patterning. Using representational difference analysis to identify genes that are differentially expressed on the left and right sides of the chick embryo, we cloned chick Claudin-1, an integral component of epithelial tight junctions. Here, we demonstrate that retroviral overexpression of Claudin-1, but not Claudin-3, on the right side of the chick embryo between HH stages 4 and 7 randomizes the direction of heart looping. This effect was not observed when Claudin-1 was overexpressed on the left side of the embryo. A small, but reproducible, induction of Nodal expression in the perinodal region on the right side of the embryo was noted in embryos that were injected with Claudin-1 retroviral particles on their right sides. However, no changes in ...
The tumor suppressor p53 is often inactivated in breast cancer cells because the overexpression of its repressors (e.g., MDM2 and MDMX). Restoration of p53 activity by small molecules through counteracting...Full Text Available
Microarray is a powerful tool for genome-wide gene expression analysis. In microarray expression data, often mean and variance have certain relationships. We present a non-parametric mean-variance smoothing...Full Text Available
Difficulty in recalling the names of people is very common in the early stages of Alzheimer's disease and in mild cognitive impairment (MCI). However, it is not known whether the difficulty in naming people in MCI reflects problems associated with lexical access or with semantic access. The aims of the present study were to investigate semantic and phonological access to proper names by use of a Tip-of-the-tongue (TOT) task in individuals with multidomain amnestic MCI, individuals with amnestic MCI, and healthy controls, as well as to study the relationships between TOT production and performance in a free recall verbal memory test. In the individuals with multidomain amnestic MCI, the main process affected was phonological access; failures in phonological access were related to deficits i...
Ethnopharmacological relevance: Extracts of the roots of Scutellaria baicalensis Georgi (Labiatae) have been widely used to relieve fever related to bacterial infection and inflammatory diseases in traditional Korean medicine and have been reported to be effective in brain diseases. These experiments were conducted to examine the effects of oral administration of Scutellaria baicalensis extracts on the rescue of memory impairments induced by chronic cerebral hypoperfusion or chronic lipopolysaccharide (LPS) infusion. In addition, the underlying mechanisms of these effects were investigated. Materials and methods: In the first experiment, chronic cerebral hypoperfusion was induced in male Wister rats by bilateral common carotid artery occlusion (BCCAo). Daily administration of Scutellaria b...
Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...
BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common condition that often results in child and family functional impairments. Although there are evidence-based treatment...Full Text Available
The paralysis-by-analysis phenomenon, i.e., attending to the execution of one's movement impairs performance, has gathered a lot of attention over recent years (see Wulf, 2007,...Full Text Available
BackgroundDespite having the largest population in Africa, Nigeria has no accurate population based data to plan and evaluate eye care services. A national survey was undertaken...Full Text Available
Immunotoxicity encompasses both reduced and heightened immune function. Diverse chemicals can impair functioning of the immune system. Both monographs and books have been devoted to detailed descriptions...Full Text Available
Background and objectives: While many patients with end-stage renal disease (ESRD) have impaired physical and psychologic well-being, less is known about these health domains in patients with advanced...Full Text Available
Hip fractures are associated with a high rate of mortality and profound temporary and sometimes permanent impairment of quality of life. Current guidelines indicate that surgeons should perform surgery...Full Text Available
Oysters are permanently exposed to various microbes, and their defense system is continuously solicited to prevent accumulation of invading and pathogenic organisms. Therefore, impairment of the animal's...Full Text Available
The hippocampus is thought to coordinate memory consolidation by reactivating traces from behavioral experience when the brain is not actively processing new input. In fact, during slow-wave...Full Text Available
Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral...Full Text Available
The increasing demand for molecular diagnostics in clinical microbiology laboratories necessitates automated sample processing. In the present study, we evaluated the performance of the MagNA Pure LC...Full Text Available
The authors’ objective was to analyze the impact of respiratory impairment on the risk of physical functional limitations among adults with chronic obstructive pulmonary disease (COPD)....Full Text Available
The juxtacapsular BNST (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of...Full Text Available
With the advent of subgenomic hepatitis C virus (HCV) replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured...Full Text Available
Background and objectives: Chronic kidney disease (CKD) is associated with impaired physical activity. However, it is unclear whether the associations of physical activity with mortality are modified...Full Text Available
BackgroundZibotentan (ZD4054) is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated...Full Text Available
BackgroundSeveral aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption...Full Text Available
Cognitive rehabilitation is an effective intervention for addressing cognitive impairments in patients with schizophrenia. Previous research has shown that the early application of Cognitive...Full Text Available
The effects of paeoniflorin (PF), a compound isolated from Paeony radix, on neurological impairment and histologically measured infarction volume...Full Text Available
BackgroundMutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial...Full Text Available
The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in patients with impaired CD4+ T cell function, particularly those with AIDS. To identify...Full Text Available
We describe an Ebolavirus minigenome-based system that is suitable for high-throughput screening of compounds able to impair Ebolavirus virus replication and/or transcription....Full Text Available
Background:In recent years, breast cancer (BC) mortality rates have declined, reflecting advances in early detection. Prevention and management of treatment sequelae that could impair...Full Text Available
Less than half of older adults with depression achieve remission with antidepressant medications, and rates of remission are even poorer for those with comorbid conditions. Psychosocial interventions...Full Text Available
BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available
Sensory analysis studies are critical in the development of quality enhanced crops, and may be an important component in the public acceptance of genetically modified foods. It has recently been established...Full Text Available
BackgroundMethamphetamine (METH), an addictive psycho-stimulant drug with euphoric effect is known to cause neurotoxicity due to oxidative stress, dopamine accumulation and glial...Full Text Available
OBJECTIVE: To assess the motor function of the left, supposedly unaffected, limbs of patients with an acute right vascular hemiplegia. METHODS: Fifteen patients with an acute vascular right hemiplegia...Full Text Available
Mass mortalities among seals and dolphins inhabiting contaminated marine regions have led to speculation about a possible involvement of immunosuppression associated with environmental pollution. To...Full Text Available
Life history theory proposes that early-life cues induce highly integrated responses in traits associated with energy partitioning, maturation, reproduction, and aging such that the individual phenotype...Full Text Available
SUMMARYDendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter....Full Text Available
Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit...Full Text Available
Chemical genetics is an emerging approach to investigate the biology of host-pathogen interactions. We screened several inhibitors of ATP-dependent DNA motors and detected the gyrase B inhibitor coumermycin...Full Text Available
ObjectiveTo investigate the impact white matter hyperintensities (WMH) detected on MRI have on motor dysfunction and cognitive impairment in non-demented elderly...Full Text Available
ContextFatigue is the most common sequela among non-small cell lung cancer (NSCLC) survivors 1–6 years post-treatment and is associated with functional limitations.Full Text Available
Obesity is a risk factor for stroke and neurodegenerative disease. Excess body fat has been linked to impaired glucose metabolism, insulin resistance, and impulsivity and may be a precursor to decline...Full Text Available
The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated in an animal model. Recovery from lobar pneumococcal pneumonia as a result of penicillin therapy...Full Text Available
BackgroundHip fracture patients often have an impaired nutritional status at the time of fracture, which can result in a higher complication rate, prolonged rehabilitation time and...Full Text Available
Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the...Full Text Available
Depending on the location, dermatoses can produce blemishes that severely impair quality of life and require highly effective treatment that is otherwise used for extensive skin involvement. We report...Full Text Available
Ammonium sulfate is produced from spent sulfuric acid from the production of alcohols. Certain mineral and organic impurities exist in the sulfuric acid that impair the quality of the ammonium sulfate. A detailed method for the chemical analysis for the impurities is presented.
BackgroundSexual function is impaired in women with inflammatory bowel disease (IBD) as compared to normal controls. We examined disease specific determinants of different aspects...Full Text Available
Merozoite surface proteins have been implicated in the initial attachment to the host red blood cell membrane that begins the process of invasion, an important step in the life cycle of the malaria...Full Text Available
Diabetic pregnancies are characterized by chronic metabolic insults, including iron deficiency, that place the developing brain at risk and for memory impairment later in life. A behavioral...Full Text Available
BackgroundEvent-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills...Full Text Available
BackgroundInadequate platelet inhibition despite aspirin and clopidogrel therapy during and after a percutaneous coronary intervention is associated with an impaired clinical outcome....Full Text Available
BackgroundFabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous...Full Text Available
BackgroundKinematic and kinetic measurements used in laboratory settings can quantify upper extremity movement impairment following stroke, but their relationship...Full Text Available
Lack of understanding about workflow can impair health IT system adoption. Observational techniques can provide valuable information about clinical workflow. A pilot study using direct observation was...Full Text Available
BackgroundIn vitro data suggest that changes in myocardial substrate metabolism may contribute to impaired myocardial function in diabetic cardiomyopathy (DCM)....Full Text Available
Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD)....Full Text Available
It is well established that changes to the chemical environment can impair development, physiology and reproductive biology; by contrast, impacts on communication have not been widely reported. This...Full Text Available
IntroductionMale circumcision is being promoted for HIV prevention in high-risk heterosexual populations. However, there is a concern that circumcision may impair...Full Text Available
BackgroundTraffic injuries can cause physical, psychological, and economical impairment, and affected individuals may also experience shortcomings in their post-accident care and...Full Text Available
... (v) Import onto or keep on Wake Island any plant or animal not indigenous to the island, other than military working dogs or a guide dog for the blind or visually-impaired accompanying its owner; or (w) Import or bring onto or...
...1) A privately owned motor vehicle. (2) A privately owned boat. (3) An indigenous animal, military working dog, or guide dog for the blind or visually-impaired accompanying its owner. (4) A narcotic or dangerous drug or...
...retardation, behavioral disorders or...blood. (3) Health protection goals...protecting your health. You are strongly...an independent analysis. The two...impairment of health. One of...although most cases of lead-induced...in the form of behavioral...
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 ...
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and proper development of ...
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...
Some of the known toxic effects of lead in mammals including man are, impaired heme synthesis, anemia, nepatopathy, nephropathy, behavioral disorders and neuropathy. However, very little is known about the effect of lead on endocrine physiology. Some data are available on lead induced impairment of thyroid function in occupationally exposed men and experimental rats. As lead nitrate is largely consumed through water and food, in this study the wild rodents Funambulus pennanti were administered lead through their drinking water and their thyroid structure, radioiodine 131-I percentage uptake and protein bound iodine (PBI) level were assessed.
Laccases are increasingly being used in food industry for production of cost-effective and healthy foods. To sustain this trend widespread availability of laccase and efficient production systems have to be developed. The present paper delineate the recent developments that have taken place in understanding the role of laccase action, efforts in overexpression of laccase in heterologous systems, and various cultivation techniques that have been developed to efficiently produce laccase at the industrial scale. The role of laccase in different food industries, particularly the recent developments in laccase application for food processing, is discussed. PMID:21048859
Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and ?-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. ...
Astrocyte dysfunction is implicated in course of various age-related neurodegenerative diseases. Chronic injection of D-galactose can cause a progressive deterioration in learning and memory capacity and serve as an animal model of aging. To investigate the involvement of astrocytes in this model, oxidative stress biomarkers, biochemical and pathological changes of astrocytes were examined in the hippocampus of the rats with six weeks of D-galactose injection. D-galactose-injected rats displayed impaired antioxidant systems, an increase in nitric oxide levels, and a decrease in reduced glutathione levels. Consistently, western blotting and immunostaining of glial fibrillary acidic protein showed extensive activation of astrocytes. Double-immunofluorescent staining further showed activated astrocytes highly expressed inducible nitric oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes, especially in the aggregated area of synapse and ...
Objectives: Many youth with tics experience distress about having tics and how others may perceive them. Such symptoms are often more impairing and distressing than are the tics and negatively impact self-concept, functioning, and quality of life. Although treatments exist that target the frequency and severity of tics, no intervention has been developed that helps youth with tics cope with their condition and limit associated functional impairment and distress. Given this, we developed a cognitive-behaviorally oriented psychotherapy protocol that promotes adaptive coping and resiliency among youth with tics in addressing varied issues commonly experienced by this population. This poster reports data from the Phase I component of this study. Method: Phase I concentrated on developing the t...
Olfactory memory dysfunctions were investigated in the triple-transgenic murine model of Alzheimer's disease (3x Tg-AD). In the social transmission of food preference test, 3x Tg-AD mice presented severe deficits in odor-based memory, without gross changes in general odor-ability. Ab and tau immunoreactivity was not observed in the primary processing regions for odor, the olfactory bulbs (OBs), whereas marked immunostaining was present in the piriform, entorhinal, and orbitofrontal cortex, as well as in the hippocampus. Our results suggest that the impairment in olfactory-based information processing might arise from degenerative mechanisms mostly affecting higher cortical regions and limbic areas, such as the hippocampus.
The dramatic increase in diagnostic rates of bipolar disorder in children and adolescents in the USA has led to an intense interest in the phenomenology of the disorder. Here we present data from a newly-developed instrument to assess episodic mania-like symptoms in youth in a large population-based sample (N?=?5326) using parent- and self-report. We found that a substantial proportion of children screened positive for having episodes of ?going high? and were at an increased risk for morbidity and impairment. Using factor analysis, we identified that episodic mania-like symptoms comprised two dimensions: An under-controlled dimension that was associated with significant impairment, and a low-risk exuberant dimension. Using latent class analysis, we identified a small group of children scor...
The integral membrane protein synaptophysin is one of the most abundant polypeptide components of synaptic vesicles. It is not essential for neurotransmission despite its abundance but is believed to modulate the efficiency of the synaptic vesicle cycle. Detailed behavioral analyses were therefore performed on synaptophysin knockout mice to test whether synaptophysin affects higher brain functions. We find that these animals are more exploratory than their wild type counterparts examining novel objects more closely and intensely in an enriched open field arena. We also detect impairments in learning and memory, most notably reduced object novelty recognition and reduced spatial learning. These deficits are unlikely caused by impaired vision, since all electroretinographic parameters measur...
Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage was independent on NO formation and involved the IFN-gamma signalling pathway as well as induction of apoptosis. If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC damage and disturbance of the epithelial integrity.
ObjectivesVaricocele is a common cause of infertility, and varicocele-associated testicular hypotrophy has been described as a potential cause of decreased semen quality. We investigated the relationship between testicular hypotrophy and poor semen quality in infertile men with varicoceles. We hypothesized that bilateral hypotrophy is required before the semen quality is severely impaired.MethodsWe retrospectively identified consecutive patients with palpable varicoceles undergoing an infertility evaluation at a single academic center. Each patient was evaluated by the same clinician with history and physical examination. Testicular hypotrophy was defined as a size discrepancy of greater than 3 mL or an absolute size of less than 14 mL. Multivariate logistic regression analysis was used to...
Purpose To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Methods Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular KATP (PNU-37883A) or BKCa [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-?B) was assessed by electrophoretic mobility shift as...
Purpose The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancer...
Most heat shock proteins (Hsps) function as molecular chaperones that help organisms to cope with stress. Although the best empirical evidence is related to heat shock, there is evidence that Hsps and their encoding genes are involved in resistance to other ecologically relevant types of stresses such as those imposed by high population density. We quantified density-dependent gene expression of large (i.e. Hsp40, Hsc70 and Hsp90) and small (Hsp20.5, Hsp20.6 and Hsp20.7) heat shock genes in neural tissue of fifth-instar nymphs of the Australian plague locust, Chortoicetes terminifera, using reverse transcription-quantitative PCR. Locusts are of particular interest when studying the influence of stress induced by high population density since they show an extreme form of phenotypic plastici...
To address the functions of FGFR2 and FGFR3 signaling during mandibular skeletogenesis, we over-expressed in the developing chick mandible, replication-competent retroviruses carrying truncated FGFR2c or FGFR3c that function as dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS-dnFGFR3 between HH15 and 20 led to reduced proliferation, increased apoptosis, and decreased differentiation of chondroblasts in Meckel's cartilage. These changes resulted in the formation of a hypoplastic mandibular process and truncated Meckel's cartilage. This treatment also affected the proliferation and survival of osteoprogenitor cells in osteogenic condensations, leading to the absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2 between HH15 and 20 or R...
Heme peroxidases are a class of multifunctional redox-active proteins found in all organisms. We recently cloned, expressed, and characterized an ascorbate peroxidase from Leishmania major (LmAPX) that was capable of detoxifying hydrogen peroxide. Localization studies using green fluorescent protein fusions revealed that LmAPX was localized within the mitochondria by its N-terminal signal sequence. Subcellular fractionation analysis of the cell homogenate by the Percoll density-gradient method and subsequent Western blot analysis with anti-LmAPX antibody further confirmed the mitochondrial localization of mature LmAPX. Submitochondrial fractionation analysis showed that the mature enzyme (?3.6?kDa shorter than the theoretical value of the whole gene) was present in the intermembrane space ...
One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine whether the chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058, a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis with [{sup 125}I]-VEGF resulted in a K {sub d} of 0.1 nM. Internalization assays indicate the preserved ligand induced internalization and metabolization of the tracer. Biodistribution studies with [{sup 123}I]-VEGF in wild type and A2058 tumor-bearing athymic mice showed low background activity and a tumor to reference tissue ratio of maximum 6.12. These results suggest that [{sup 123}I]-VEGF is a potentially suitable tracer for tumor therapy evaluation.
Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas. SRS seems to be superior to other non-invasive imaging modalities and has been proven to significantly contribute to patient management. However, the sensitivity depends on the size and exact localization of the tumors. Smaller lesions and lesions located in the duodenum show a significantly lower sensitivity. In any case, SRS belongs to the routine imaging procedure for gastrinomas for localization and staging and can also be used for evaluation of the tumor progression. (author)
Increasing evidence has been accumulated indicating the important role of epigenetic regulation in tumor genesis. Previously, we observed that the transfection of hepatitis C virus core (HCVc) protein led to malignant transformation in normal biliary cells, and that tumor suppressor gene RASSF1A was downregulated in many hilar cholangiocarcinoma patients by hypermethylation in the promoter region. In the present study, we found SET and MYND domain-containing protein 3 (SMYD3), a novel histone methyltransferase, was overexpressed in cholangiocarcinoma patients especially in those with HCV infection. Transfection of HCVc into hilar cholangiocarcinoma cell lines QBC939 and FRH0201 could upregulate the expression of SMYD3 and promote cell growth, which was consistent with the results of our cl...
2-methylpropan-1-ol (isobutanol) is a leading candidate biofuel for the replacement or supplementation of current fossil fuels. Recent work has demonstrated glucose to isobutanol conversion through a modified amino acid pathway in a recombinant organism. Although anaerobic conditions are required for an economically competitive process, only aerobic isobutanol production has been feasible due to an imbalance in cofactor utilization. Two of the pathway enzymes, ketol-acid reductoisomerase and alcohol dehydrogenase, require nicotinamide dinucleotide phosphate (NADPH); glycolysis, however, produces only nicotinamide dinucleotide (NADH). Here, we compare two solutions to this imbalance problem: (1) over-expression of pyridine nucleotide transhydrogenase PntAB and (2) construction of an NADH-de...
Guar seed gum, consisting primarily of a high molecular weight galactomannan, is the most cost effective natural thickener, having broad applications in the food, cosmetics, paper, pharmaceutical and petroleum industries. The properties of the polymer can potentially be enhanced by genetic modification. Development of suitable endosperm-specific promoters for use in guar is desirable for metabolic engineering of the seed gum. A ~1.6?kb guar mannan synthase (MS) promoter region has been isolated. The MS promoter sequence was fused with the GUS reporter gene and overexpressed in the heterologous species alfalfa (Medicago sativa). The potential strength and specificity of the MS promoter was compared with those of the constitutive 35S promoter and the seed specific ?-phaseolin promoter. Quant...
Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...
Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated....Full Text Available
... The award is named for the late Samuelson, a leader and advocate for upward mobility and placement programs to enable visually impaired and blind persons to lead productive lives. The award was created to recognize the career achievements and accomplishments of employees who work in a NIB-associated agency. The Chicago Lighthouse, the company for which Uken works, nominated him based on his exceptional performance at CERL as ...
During protein synthesis, aminoacyl-tRNA (aa-tRNA) and release factors 1 and 2 (RF1 and RF2) have to bind at the catalytic center of the ribosome on the 50S subunit where they take part in peptide bond...Full Text Available
Despite successful reduction of the general lead exposure, this heavy metal is still a matter of public concern due to the fact that associations with intellectual impairment or delayed puberty are found to correlate with very low lead blood concentrations. Lead in tap water is still an important contribution to lead exposure which may cause health risk for infants. Therefore, lead pipes should be completely sanitated by exchange against pipes made from more healthy materials. (orig.)
Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from...Full Text Available
BackgroundGeneralized anxiety disorder (GAD) is the most frequent anxiety disorder in primary care patients. It is known that painful physical symptoms (PPS) are associated with...Full Text Available
Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis....Full Text Available
The impact of a single seizure on cognition remains controversial. We hypothesized that a single early life seizure (sELS) on rat post-natal day (P) 7 would alter only hippocampal-dependent...Full Text Available
Sprengel deformity is a congential malformation with usually unilateral elevation and medial rotation of the scapula. An omovertebral bone is generally present. Associated skeletal malformations are frequently present. Though functional impairment is mild, the cosmetic and psycho-social impairment can be considerable. The prognosis of early surgical therapy is good. The presented case also justifies surgical correction in the older child. (orig.) [German] Die Sprengel-Deformitaet ist eine angeborene Fehlbildung mit meist einseitiger Elevation und Medialrotation der Skapula. Meist ist ein Os omovertebrale vorhanden. Assoziierte skelettale Fehlbildungen sind haeufig. Obgleich funktionell wenig einschraenkend, ist die kosmetische und psycho-soziale Beeintraechtigung oft erheblich. Die Prognose der fruehen operativen Therapie ist gut. Der vorliegende Fall ermutigt zur operativen Therapie auch im hoeheren Kindesalter. (orig.)
We investigated the effect of irradiation on the kinetic characteristics of amino acid and glucose transport, and the effect on the activity of the cell membrane-bound enzyme 5'-nucleotidase and on the receptor-mediated stimulation of cyclic adenosine monophosphate synthesis by prostaglandin E1. Irradiation inhibited the sodium-dependent amino acid transport by a reduced binding of the amino acid to the transport unit. The transport of glucose, which appeared to be a sodium-independent process, was temporarily stimulated by increased maximal velocity of the transport. No effect was found on the binding to the transport unit. Irradiation increased the 5'-nucleotidase activity and decreased the prostaglandin E1-stimulated cyclic adenosine monophosphate synthesis 48 h after exposure to 20 Gy. It is concluded that irradiation decreases sodium-dependent transport by impairment of the transport unit, does not impair a ...
Cerebral maturation in the human fetal brain was investigated by in utero localized proton magnetic resonance spectroscopy (MRS). Spectra were acquired on a clinical MR system operating at 1.5 T. Body phased array coils (four coils) were used in combination with spinal coils (two coils). The size of the nominal volume of interest (VOI) was 4.5 cm"3 (20 mm x 15 mm x 15 mm). The MRS acquisitions were performed using a spin echo sequence at short and long echo times (TE = 30 ms and 135 ms) with a VOI located within the cerebral hemisphere at the level of the centrum semiovale. A significant reduction in myo-inositol and choline and an increase in N-acetylaspartate were observed with progressive age. The normal MR spectroscopy data reported here will help to determine whether brain metabolism is altered, especially when subtle anatomic changes are observed on conventional images. Some examples of impaired fetal brain development studied by MRS are illustrated.
Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. ...
Cerebral blood flow (CBF) was measured by the "1"3"3Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands ...
Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. Our data suggest that ...
Autism is a pervasive developmental condition, characterized by impairments in non-verbal communication, social relationships and stereotypical patterns of behavior. A large body of evidence suggests that several aspects of face processing are impaired in autism, including anomalies in gaze processing, memory for facial identity and recognition of facial expressions of emotion. In search of neural markers of anomalous face processing in autism, much interest has focused on a network of brain regions that are implicated in social cognition and face processing. In this review, we will focus on three such regions, namely the STS for its role in processing gaze and facial movements, the FFA in face detection and identification and the amygdala in processing facial expressions of emotion. Much evidence suggests that a better understanding of the normal development of these specialized regions is essential for discovering the neural bases of face ...
Emerging evidence suggests that E3 ligases play critical roles in diverse biological processes, including innate immune responses in plants. However, the mechanism of the E3 ligase involvement in plant innate immunity is unclear. We report that a rice gene, OsBBI1, encoding a RING finger protein with E3 ligase activity, mediates broad-spectrum disease resistance. The expression of OsBBI1 was induced by rice blast fungus Magnaporthe oryzae, as well as chemical inducers, benzothiadiazole and salicylic acid. Biochemical analysis revealed that OsBBI1 protein possesses E3 ubiquitin ligase activity in vitro. Genetic analysis revealed that the loss of OsBBI1 function in a Tos17-insertion line increased susceptibility, while the overexpression of OsBBI1 in transgenic plants conferred enhanced resi...
Pancreatitis-associated protein (PAP) is a secretory pancreatic protein present in small amounts in normal pancreas and overexpressed during the acute phase of pancreatitis. In this paper, the authors describe the cloning, characterization, and chromosomal mapping of the human PAP gene. The gene spans 2748 bp and contains six exons interrupted by five introns. The gene has a typical promoter containing the sequences TATAAA and CCAAT 28 and 52 bp upstream of the cap site, respectively. They found striking similarities in genomic organization as well as in the promoter sequences between the human and rat PAP genes. The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization. This localization coincides with that of the reg/lithostathine gene, which encodes a pancreatic secretory protein structurally related to PAP, suggesting that both genes derived from the same ancestral gene by duplication. 35 refs., 4 ...
Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) was used to identify the effects of GPC3 on the regulation of malignant behaviors of HCC. MHCC97-H, a highly metastatic human HCC cell line in which GPC3 mRNA and protein levels were detected as the highest among the 4 HCC cell lines assessed in this study, and was thus selected as a cell model for in vitro and in vivo experiments. The results showed that down-regulation of GPC3 can significantly inhibit the proliferative and invasive ability of MHCC97-H. Compared with the parental HCC cells, GPC3-silenced cells exhibited attenuated capacities in developing tumors in nude mice, while the growth of tumor xenografts derived from these cells dramatically ...
Purpose HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule ZHER2:342 is a small (7?kDa) affinity protein binding to HER2 with an affinity of 22?pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of ZHER2:342 and to compare the targeting properties of monomeric and dimeric forms of ZHER2:342. Methods The biodistribution of different radioiodinated derivatives of ZHER2:342 was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of 125I-PIB-ZHER2:342 and site-specifically labelled 125I-HPEM-ZHER2:342-C were compared. Biodistributions of monomeric 131I-HPEM-ZHER2:342-C and dimeric 125I-HPEM-(ZHER2:342)2-C were evaluated using a paire...
Abstract Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome-wide association studies, but little is known about their effects on survival. SMAD7 regulates gastrointestinal inflammation by inhibiting transforming growth factor- (TGFB), which can act as both a tumor suppressor and a promoter of metastasis. Regular use of cyclooxygenase-2 (COX2) inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), reduces the risk of developing CRC. Because COX2 overexpression reduces the growth suppressing effects of TGFB, we hypothesized that survival may depend on both SMAD7 genotype and prediagnostic NSAID use. Postmenopausal women, ages 50-74, diagnosed with incident invasive CRC from 1997 to 2002 were identified using t...
Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...
The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or paraquat-induced damage) because such compounds are able to potentiate the cell-killing or cell ...
Structural instability of wild-type fibroblast growth factor (FGF)-1 and its dependence on exogenous heparin for optimal activity diminishes its potential utility as a therapeutic agent. Here we evaluated FGFC, an FGF1:FGF2 chimeric protein, for its receptor affinity, absolute heparin-dependence, stability and potential clinical applicability. Using BaF3 transfectants overexpressing each FGF receptor (FGFR) subtype, we found that, like FGF1, FGFC activates all of the FGFR subtypes (i.e., FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b and FGFR4) in the presence of heparin. Moreover, FGFC activates FGFRs even in the absence of heparin. FGFC stimulated keratinocytes proliferation much more strongly than FGF2, as would be expected from its ability to activate FGFR2b. FGFC showed greater struct...
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...
Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...
The utilization of nuclear medicine bone scanning examinations early in the diagnostic process allows physicians to render prompt and correct treatment in urgent or difficult athletic cases. Bone scanning should be performed for athletic injuries whenever (1) x-rays are normal but bone or joint pain persists; (2) x-rays are positive but it cannot be determined if the findings are acute or chronic; (3) soft-tissue injuries present and x-rays are not useful; and (4) bone pain or joint impairment present without a history of trauma.89 references.
Dyspnea is the most distressing symptom experienced by those suffering from advanced stages of chronic obstructive pulmonary disease (COPD). Activity-related dyspnea in COPD is multifactorial but is associated with increased central neural drive, impaired dynamic respiratory mechanics and abnormal respiratory muscle function. Each of these components can potentially be targeted for pharmacotherapy. Recent advances in the pharmacotherapy of COPD include the development of new long-acting bronchodilators which, when combined, provide sustained improvements in dyspnea. Additionally, novel applications of older therapies such as opiates, furosemide, helium-oxygen, and statins show early promise as dyspnea-relieving interventions in COPD. Effective pharmacological manipulation of the affective ...
The viability of osteocytes can be demonstrated in sawn decalcified sections of bone by their lactate dehydrogenase activity. In the cancellous bone of the femoral head, the proportion of lacunae containing viable osteocytes decreased from 88 +/- 7% (mean +/- SD) at 10-29 years to 58 +/- 12% (P Ultimate compressive strength did not correlate with osteocyte viability. In the femoral head there is gradual, age-related reduction in osteocyte viability that can be more pronounced in hip fracture. Osteocyte death may affect bone quality by impairing repair of fatigue damage. PMID:8275364
The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.
Inhaled beryllium oxide results in impaired alveolar clearance of inhaled "2"3"9PuO_2 and induces an inflammatory reaction in the lung. However, only one of 184 rats exposed to beryllium developed a lung tumor; none of 128 unexposed rats developed a lung tumor. Fifty-six lung tumors were induced in 181 rats exposed to plutonium. A total of 37 lung tumors were found in 119 rats given combined exposures to beryllium and plutonium. Only in rats given the highest levels of both beryllium and plutonium was there an incidence of lung tumors greater than that seen with exposure to plutonium only.
Back pain from osteoporosis is commonly related to compression fractures. The patient with vertebral compression fractures additionally suffers from an ongoing risk of recurrent fractures and postural abnormalities that can result in impaired respiratory function, leading to increased risk of morbidity. Weakened back muscles, especially the back extensor group, are felt to contribute significantly to this risk. The combination of pharmacologic and nonpharmacologic interventions, through physical activity, exercise, and modalities, are potential interventions that could be used to help reduce the pain of osteoporotic compression fractures as well as potentially reducing recurrent fracture rates.
Cell voltage monitoring (CVM) systems are essential for the operation of fuel cell stacks and some battery systems, in the field as well as in the laboratory, because they allow the diagnosis and correction of problems that would otherwise go unnoticed and cause impaired performance or even permanent damage. A robust, safe, and low-cost design for a CVM unit is presented, using electromechanical relays as multiplexing switches. Some examples from the application of the unit on the University of Delaware's fuel cell battery hybrid buses are presented, including its use in automatically correcting anode flooding and diagnosing air channel blockage. (author)
Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Although there is a rich literature on these systems, parasitoid immune-disabling mechanisms have not been fully elucidated. Here we report on a newly discovered immune-disabling mechanism in the Pieris rapae/Pteromalus puparum host/parasitoid system. Because venom injections and parasitization suppresses host phagocytosis, we turned attention to the P. rapae scavenger receptor (Pr-SR), posing the hypothesis that P. puparum venom suppresses expression of the host Pr-SR gene. To test our hypothesis, we cloned a full-length cDNA of the Pr-SR. Multiple sequences alignment showed the deduced amino acid sequence of Pr-SR is similar to scavenger receptors of other lepidopterans. Bacterial and bead injections induced Pr-SR mRNA and protein expression, which peaked at 4h post-bead injection. Venom injection inhibited Pr-SR ...
The present study investigated sex differences and the effect of a high level of estradiol in the female meadow vole on performance in the forced swim test (FST) and the Morris water maze in meadow voles. Female meadow voles were ovariectomized (OVX) and administered either vehicle (sesame oil) or estradiol for 2 days prior to performing the FST. Four days following the FST, all animals were run in the Morris water maze. Results indicated that estradiol-injected female meadow voles showed more 'depressive-like' behaviors in the FST (greater time spent immobile and less time spent swimming) than vehicle-treated female or male meadow voles. In addition, estradiol-treated females had impaired performance (greater latencies and distance swam to reach the hidden platform) than both vehicle-treated female and male meadow voles, consistent with previous data. Despite the fact that estradiol administration increased 'depressive-like' behaviors in the FST and ...
Clinical and hormonal indices of androgenic activity were compared in 118 males chronically intoxicated with alcohol. The population was divided into two groups with respect to their clinical and hormonal androgenic indices: 76 patients with (Group 1), and 46 patients without (Group 2) androgenic insufficiency. Distinct signs and syndromes of alcohol addiction were shown to correlate with the extent of cross-regulation impairment within hypothalamo-hypophyseo-gonadal system. This was particularly derived from comparison of clinical picture of chronic alcohol intoxication and hormone activity in the groups. Conventional therapy failed to restore the neuroendocrine indices that was apparently due to inhibition of cross-regulation links in the hypothalamo-hypophyseo-gonadal system at several stages of alcohol addiction. PMID:3223149
Agricultural runoff is a major non-point source pollutant and is the leading impairment of streams and rivers in the USA. This study examined the effects of agricultural, forest and urban land cover on water quality at the watershed level. Forty-three catchments ranging from 12 to 50?km2 were selected based on a land cover gradient within Lower Kaskaskia River Watershed in Illinois. Grab samples were collected and analyzed for nutrients, bacteria, and total suspended solids (TSS). Forest land cover was included in six of the ten regression models produced. Four of these regression models were for base flow conditions, suggesting that forest land cover had a significant impact on base flow water quality. Urban land cover was also included in six of the regression models. However, the majori...
Primary objective: Acquired brain injury (ABI) is associated with significant cognitive, behavioural, psychological and physical impairment. Hence, it has been important to leverage assessment approaches in rehabilitation by using current and emerging technologies, including virtual reality (VR). A number of VR rehabilitation programmes have been designed in recent years, mainly to improve upper limb function. However, before this technology gains widespread use, evaluation of the scientific evidence supporting VR-assisted rehabilitation is needed. The present review aimed to assess the rationale, design and methodology of research investigating the clinical impact of VR on ABI upper-limb rehabilitation. Research design: A total of 22 studies were surveyed using a Cochrane-style review. Re...
Purpose: To enable the use of a vacuum container under a relatively high temperature or a high level radioactive dose. Constitution: Vacuum sealing materials for use in a vacuum container are made of resins such as polyimide and polyamide. The sealing materials are joined to the both surfaces of a plate-like insulator by means of adhesives or sealants, or the sealing materials are joined between two plate-like insulators by means of adhesives or sealants. They are situated within grooves of both of flanges, which are clamped tightly by insulation bolt and nut. Since the vacuum sealing materials are joined to the insulator by means of the adhesives or sealants, the reliability of the vacuum sealing can be improved without impairing the electrical insulation. The resin of the vacuum sealing material can be used for the radiation dose up to 10"8 rad, temperature up to 250"0C or more. (Seki, K.).
Abstract Toll-like receptor 2 (TLR2) is an immune sensor for gram-positive bacterial cell wall components. Single-nucleotide polymorphisms (SNPs) in the TLR2 gene that impair its function may, therefore, influence the risk and outcomes of gram-positive bacterial infections. In a cohort of 694 liver transplant recipients, we assessed the TLR2 SNP that is translated into an amino acid substitution of arginine for glutamine at position 753 (R753Q), and we found that its presence was associated with the clinical characteristics and outcomes of gram-positive bacterial infections. The proportions of patients with the TLR2 R753Q SNP did not significantly differ between those with gram-positive bacterial infections and those without gram-positive bacterial infections (9.6% versus 9.6%, P = 0.999)....
The extent to which a novel wash-off process using polyamide beads removed five different types of dye from three different types of fibre was similar to that achieved using conventional aftertreatments. Whilst bead wash-off and the conventional aftertreatments were of similar duration and temperature, conventional aftertreatment employed a 10:1 or 20:1 liquor ratio whereas bead wash-off used a < 1:1 liquor ratio. As vagrant dye was adsorbed onto the bead material during wash-off, the low amount of wastewater generated contained little residual dye, thereby offering the potential of reduced environmental and cost benefits. Bead wash-off did not impair the fastness of two non-metallised acid dyes on nylon 6,6 to washing at 60 ?C.
Patients with acute myocardial infarction (AMI) and diabetes mellitus, as well as patients admitted with elevated blood glucose without known diabetes, have impaired outcome. Therefore intensive glucose-lowering therapy with insulin (IGL) has been proposed in diabetic or hyperglycaemic patients and has been shown to improve survival and reduce incidence of adverse events. The current manuscript provides an overview of randomised controlled trials investigating the effect of IGL. Furthermore, systematic glucose?insulin?potassium infusion (GIK) has been studied to improve outcome after AMI. In spite of positive findings in some early studies, GIK did not show any beneficial effects in recent clinical trials and thus this concept has been abandoned. While IGL targeted to achieve normoglycaemi...
Individuals with Asperger syndrome (AS) have problems in following conversation, especially in the situations where several people are talking. This might result from impairments in audiovisual speech perception, especially from difficulties in focusing attention to speech-relevant visual information and ignoring distracting information. We studied the effect of visual spatial attention on the audiovisual speech perception of adult individuals with AS and matched control participants. Two faces were presented side by side, one uttering /aka/ and the other /ata/, while an auditory stimulus of /apa/ was played. The participants fixated on a central cross and directed their attention to the face that an arrow pointed to, reporting which consonant they heard. We hypothesized that the adults wi...
Changes in the supply situation have necessitated the use of poorly-caking coals in blends for blast furnace coke. This has led to impairment of the coke rate (up to 9 kg/t iron) and furnace throughput (down 3.8%). Coke strength has suffered and leads to difficulties in the hearth area. Despite maintained pressure gradient between throat and tuyeres, blast figures were lower, suggesting decreased permeability of the charge and a general deterioration in heat utilization. Coke breeze became excessive and had to be removed on several occasions. Other factors which may be involved include the graphitization of the coke and its combustibility, neither of which were included in this study; coke quality, however, remains of prime importance to projected increases in furnace capacity.
A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...
The growing epidemic of juvenile obesity has prompted pediatricians to investigate obesity-related conditions in obese teenagers. We report a clinical case of severe hepatic fibrosis in an adolescent with severe and recent obesity. Because of elevated serum aminotransferase levels, abnormal hepatic ultrasonography and insulin resistance (impaired glucose tolerance), we suspected nonalcoholic steatohepatitis (NASH). Disease activity and fibrosis were confirmed on liver biopsy. Considering the risk of progression toward cirrhosis and its complications, and the pathological liver lesions, we started long-term medical monitoring and drug therapy to control weight loss. At present, although biopsy is the only validated way to establish the diagnosis of NASH, there is no consensus on its indicat...
Soluble TWEAK is a member of the TNF-alpha family of cytokines that has been shown to predict mortality in patients with heart failure. Pulmonary artery hypertension is a devastating disease, in which right ventricular function has been shown to be the major determinant of prognosis. In this hypothesis-generating study, we sought to evaluate the potential usefulness of sTWEAK in the prediction of disease severity in patients with pulmonary artery hypertension. We therefore conducted a retrospective analysis of sTWEAK serum levels in 95 stable patients with PAH. For all patients data on hemodynamic parameters, biomarkers and functional exercise tests were available. Compared to controls, patients with PAH showed significantly decreased levels of sTWEAK [median 314?pg/ml (interquartile range...
Severe affective and behavioral dysregulation, labeled as severe mood dysregulation (SMD), is a widely spread phenomenon among adolescent psychiatric patients. This phenotype constitutes severe impairment across multiple settings, including various symptoms, such as non-episodic anger, mood instability, and hyperarousal. Moreover, SMD patients often show depression and reduced need for sleep. Despite a lifetime prevalence of 3.3%, systematic research is still scarce, and treatments that have been established do not account for the range of symptoms present in SMD. Considering the circadian dysfunctions, two hormones, melatonin and cortisol, are essential. When these hormones are dysregulated, the circadian rhythm gets out of synchrony. Since evidence is emerging showing that the worse the ...
One hypothesis for the decline of the North American greater (Aythya marila) and lesser (A. affinis) scaup population is that contaminant burdens acquired on wintering or staging areas impair reproduction or cause lethal or sublethal health effects. Recent studies have found increased selenium (Se) concentrations in scaup but have focused on the fall and spring staging periods. From January to March 2006 and December to March 2006 and 2007, we analyzed liver tissues collected from greater scaup wintering in western Lake Ontario for 16 trace elements. We also measured Se concentrations in greater scaup blood and Dreissenid mussel tissue. Se was the only trace element that occurred at increased concentrations (>10??g/g liver dry weight) in a substantial proportion (99%) of greater scaup live...
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...
A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the...
A three-light, three-lever discrete avoidance behavioral task was initiated to study the effects of a 500-675 rad neutron pulse upon performance. Eight primates performed the task for 4 h(3.5 h postexposure) on exposure day and for 4 h on each of 3 d postexposure. For the exposure day, five subjects had a decrease in correct responses, seven had increased reaction times, and six experienced productive emesis within 3.5 hours postexposure. Although the performance degradations were not severe, these data suggest that the performance of time critical tasks could be significantly impaired.
Ozone is a principal component of photochemical air pollution endogenous to numerous metropolitan areas. It is primarily formed by the oxidation of NOx in the presence of sunlight and reactive organic compounds. Ozone is a highly active oxidizing agent capable of causing injury to the lung. Lung injury may take the form of irritant effects on the respiratory tract that impair pulmonary function and result in subjective symptoms of respiratory discomfort. These symptoms include, but are not limited to, cough and shortness of breath, and they can limit exercise performance. The effects of ozone observed in humans have been primarily limited to alterations in respiratory function, and a range of respiratory physiological parameters have been measured as a function of ozone exposure in adults and children. These affects have been observed under widely varying (clinical experimental and environmental settings) conditions
Background Experimental and clinical studies have identified a crucial role of microcirculation impairment in severe infections. We hypothesized that mottling, a sign of microcirculation alterations, was correlated to survival during septic shock. Methods We conducted a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included during a 7-month period. After initial resuscitation, we recorded hemodynamic parameters and analyzed their predictive value on mortality. The mottling score (from 0 to 5), based on mottling area extension from the knees to the periphery, was very reproducible, with an excellent agreement between independent observers [kappa?=?0.87, 95% CI (0.72?0.97)]. Results Sixty patients were included. The SOFA scor...
Male infertility, characterized by hypogonadism, decreased semen quality or ejaculatory dysfunction, accounts for approximately 20% of infertility cases. Obesity and metabolic dysfunction have been identified, among other causal factors, to contribute to male infertility. In the context of the Western world's `obesity epidemic', this article discusses three main biological mechanisms linking obesity to impaired male reproductive function: hypogonadism, testicular heat stress/hypoxia-induced apoptosis and endocrine disruption by `obesogens'. Among these, obesity-induced hypogonadism is undoubtedly the most clinically significant and is easily assessed. Rapidly expanding areas of research in this area include leptin modulation of kisspeptins and hypothalamic-pituitary-testicular hormone path...
The petroleum ether fraction (PEF) from the EtOH extract of flowers and buds of Chrysanthemum indicum was evaluated on antinociception in mice using chemical and thermal models of nociception. PEF administered orally at doses of 188 and 376mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and the hot plate test. In the pentobarbital sodium-induced sleep time test and the open-field test, PEF neither enhanced the pentobarbital sodium-induced sleep time nor impaired the motor performance, indicating that the observed antinociception was unrelated to sedation or motor abnormality. In a measurement of core body temperature, PEF did not affect temper...
Abstract Objectives: This investigation reviewed experimental studies of laser irradiation of wound healing in mice and rats published from 2003 to August 2008, respectively, to assess putative stimulatory effects of this treatment. Background: Animal models, including rodents, attempt to reflect human wound healing and associated problems such as dehiscence, ischemia, ulceration, infection, and scarring. They have played a key role in furthering understanding of underlying mechanisms involved in impaired wound healing, and in testing new therapeutic strategies including laser irradiation. Method: Original research papers investigating effects of laser or monochromatic light therapy on wound healing in mice and rats and published from January 2003 to August 2008 were retrieved from library...
OBJECTIVE --To evaluate the consequences on male sexual function of intraprostatic injection of botulinum toxin type A (BoNT/A) as a treatment for benign prostatic hyperplasia (BPH). Although BoNT/A is effective in decreasing symptoms of BPH, neuronal impairment caused by the neurotoxin might affect emission/ejaculation. These aspects have not been evaluated before. PATIENTS AND METHODS --In all, 16 sexually active men aged >60 years with BPH/benign prostatic enlargement (BPE), International Prostate Symptom Score (IPSS) -8 and a maximum urinary flow rate (Qmax) <15mL/s refractory to standard medical therapy volunteered for the study. --Patients were injected transrectally, under ultrasonographic control, with 200U of BoNT/A in the prostate. Evaluation was carried out at baseline and 1, 3 ...
Abstract The heterotetrameric K++-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na++ channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection o...
The present study was designed with an aim to analyze the effect of acute aluminium phosphide (ALP) exposure (10mg/kg b.wt, intragastrically) on the kinetic characteristics of cytochrome oxidase and energy metabolism in male Wistar rat liver mitochondria. Liver mitochondrial preparations from ALP-treated rats exhibited significant decrease (66%) in the activity of cytochrome oxidase suggesting that there was a decrease in the catalytic efficiency of the active oxidase molecules on ALP treatment. The decreased activity of cytochrome oxidase with altered NADH and succinic dehydrogenase activities might have contributed towards a significant decline in state 3 and state 4 respiration as observed. These alterations in the electron transport chain complexes in turn adversely affected the ATP sy...
ObjectiveTo address the characteristics of hearing loss in patients with Turner syndrome (TS), we evaluated hearing levels of patients with TS and analyzed causative factors.Study designThirty-three patients with TS (8 to 40 years of age) were studied through the use of audiological measurements, and causative factors were explored.ResultsTwenty cases (35 of 66 ears tested) showed high-frequency (8 kHz) sensory neural hearing loss (HFQ-SNHL). Fifteen cases (26 ears) and 15 cases (24 ears) of the impaired 20 cases were unresponsive to distortion-product otoacoustic emissions and transient-evoked otoacoustic emissions, respectively. HFQ-SNHL showed little relation to the history of middle ear infection and puberty, although middle ear infections were seen in 11 of the 20 cases. The hearing t...
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...
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...
Children with attention-deficit/hyperactivity disorder (ADHD) often have poor relationships with peers. However, research on this topic has predominantly focused on boys. This study considered child gender, ADHD status, and dimensionally assessed conduct problems as predictors of peer relationship difficulties. Participants were 125 children (ages 6-10; 67% male), 63 with clinical diagnoses of ADHD and 62 non-ADHD comparison youth. Conduct problems were reported by teachers and observed in a lab playgroup. Peer relationships were assessed by parent report, teacher report, and peer sociometric nominations in the playgroup. Results suggested that children with ADHD, as well as those with high conduct problems, displayed more impaired peer relationships than did comparison children and those ...
A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. Arterial blood gas analysis gave an oxygen tension of 8.38 kPa (63 Torr). Pulmonary function testing revealed restrictive ventilatory impairment with a reduction in the diffusing capacity. The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive development by a provocation test to the humidifier water. The yeast Debaryomyces Hansenii was the only microorganism cultured from the water of the humidifier. The double diffusion precipitating test and lymphocyte proliferative response was positive for an extract of D. Hansenii, providing evidence to incriminate this fungus. This is the first described case of EAA caused by D. Hansenii. PMID:12449192
14 surgical patients with non-hepatobiliary diseases were studied with "9"9"mTc-EHIDA imaging to evaluate the effect of total parenteral nutrition (TPN) on the hepatobiliary function. Duration of TPN ranged from 6-56 days, 10 of the 14 patients Beijing within 10 days. The results showed that: (1) 11 of 14 patients had abnormal scintigraphic features. The most prominet findings were delayed liver excretion and prolonged blood clearance time. This fact suggests that not only the rate of excretion of the bile from the liver is decreased but the uptake ability of the hepatorcyte is also impaired. (2) The effect of TPN on liver function is reversible. It was concluded that in order to prevent irreversible damage of hepatobiliary function caused by TPN, the duration of TPN should not be too long and oral intake of nutrients should be resumed as soon as possible.
We have recently reported that spontaneously hypertensive rats (SHRs) exhibit a deficit in contextual fear conditioning that is specifically reversed by antipsychotic and potentiated by psychostimulants and other manipulations thought to produce schizophrenia-like states in rodents. Based on these findings, we suggested that this deficit in fear conditioning could be used as an experimental model of emotional processing impairments observed in schizophrenia. This strain has also been suggested as a model by which to study attention deficit/hyperactivity disorder (ADHD). Considering that schizophrenia and ADHD are both characterized by poor social function, this study aimed to investigate possible behavioral deficits of SHRs in a social context. Furthermore, we sought to examine the effects...
Objectives1. We will use reduction of lysosomal stability as an indicator of cell injury induced by C-60 fullerenes and carbon nanotubes in the liver analogue or digestive gland (hepatopancreas) of marine mussels. Molluscan hepatopancreatic digestive cells are key to normal function and are a sensitive key interface with the environment. Reduction of lysosomal stability is mechanistically linked with impaired health of the whole animal. 2. We will also test the hepatopancreatic digestive cells for evide [continued...]DescriptionNanotechnology is a major innovative scientific and economic growth area, which may present a variety of hazards for environmental and human health. The surface properties and very small size of nanoparticles and nanotubes provides surfaces that may bind and transport toxic chemical pollutants, as well as possibly being toxic in their own right by generating reactive oxygen species (ROS). There is a wealth of evidence for the harmful effects ...
In a series of experiments carried out on young and adult rabbits the effect of isocaloric low protein diets containing 4% or 8% protein compared with a diet containing 21% protein on Obeliscoides cuniculi infection was studied. The pathogenesis, resistance and local immunity were assessed after single infections with 10,000 larvae or reinfection with 5000 larvae. Live weight gain was reduced in young and adult rabbits fed the low protein diets, but the establishment of parasites was not substantially influenced by protein deprivation. However, development of worms in the histotrophic phase and parasite fecundity were impaired in association with the low protein diet. Moreover, mild anaemia as well as changes in the mucosal immune response as a result of infection were related to the level of dietary protein. (author). 30 refs, 6 figs, 5 tabs.
Rationale Hypothalamic?pituitary?adrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants. Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile. Aspects of neuropsychological performance, notably working memory, are susceptible to corticosteroid modulation and are impaired in depression. Aspirin has been shown to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression. Objectives To examine the effect of sub-acute (300?mg daily for 7?days) aspirin pre-treatment on the cortisol awakening response and the effect of acute (600?mg) and sub-acute aspirin on the neuroendocrine and neuropsychological response...
The presence of inefficient distribution networks and supply chains of medicines creates problems in that even if African countries can secure steep, sustainable cost-containing procurements, access to needed medicines may still be impaired. The expected health benefits from affordable pricing or subsidies on prices of medicines may not be realized. This article evaluates drug supply chains in African countries and advocates for consolidated private wholesale markets and multiplicity of retail pharmacies. Public supply chains should be shortened and supported by contracting out with private distributors, including wholesalers and retail pharmacies. Additionally, drug regulatory authorities should be allowed to charge registration fees that are proportionate to the costs of technical regula...
Immune thrombocytopenic purpura (ITP), Guillain-Barre syndrome (GBS), and Hashimotos thyroiditis (HT) are autoimmune disorders caused by impaired self-tolerance mechanisms triggered by interaction between genetic and environmental factors. ITP is an immune-mediated destruction of platelets resulting in mucocutaneous bleeding, GBS is an ascending motor paralysis caused by an inflammatory demyelination of peripheral nerves, and HT is characterized by autoimmune-mediated destruction of the thyroid gland. The concurrent development of ITP and GBS has only rarely been reported in the literature, and GBS itself rarely occurs with other autoimmune disorders. We present a 21 year-old patient with known Hashimotos hypothyroidism that simultaneously developed GBS and ITP after an upper respiratory t...
Purpose Nonpoint sources (NPS) pollution has been an important cause for water quality impairment worldwide. To take the temporal variations of both NPS pollution and in-stream attenuation into consideration, an inverse modeling approach and the load duration curve (LDC) method were combined for variable nutrient total maximum daily load (TMDL) development. Methods Water quality and hydrological parameters were monitored monthly along the ChangLe River system in 2004?2008. The catchment NPS export load (EL) and TMDL for total nitrogen (TN) were estimated by the inverse format of an existing stream nutrient transport equation. The LDC method was used to describe the variability of EL, TMDL, requiring load (RLR) and percent (the ratio between the RLR and the EL, RPR) reduction, and then to s...
Maternal stress during pregnancy, particularly that combined with low socioeconomic status (SES), has been linked to an increased risk for impaired behavioural and emotional development and affective disorders in children. In animal models, acute periods of prenatal stress have profound effects on hypothalamo-pituitary-adrenal (HPA) function and behaviour. However, few studies have determined the impact of chronic exposure to stress in animal models. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on growth, locomotor behaviour and HPA axis function in juvenile guinea pig offspring. Pregnant guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestat...
The primary goal of this study was to assess the association between the full birth weight distribution and prevalence of specific developmental disabilities and related measures of health and special education services utilization in US children. Using data from the 1997?2005 National Health Interview Survey (NHIS) Sample Child Core, we identified 87,578 children 3?17?years of age with parent-reported information on birth weight. We estimated the prevalences of DDs (attention-deficit/hyperactivity disorder [ADHD], autism, cerebral palsy, hearing impairment, learning disability without mental retardation, mental retardation, seizures, stuttering/stammering, and other developmental delay) and several indicators of health services utilization within a range of birth weight categories. We cal...
Data from a detailed evaluation of environment conditions in three U.S. Army field stations are presented. Three field stations were evaluated: Kunia, Augsburg, and Berlin. Results from a questionnaire administered to over 600 people at all sites in three job types (operator, analyst, and administrative/other) are given which indicate major concerns with conditions such as temperature, lighting, space, furniture, equipment functioning, and general environmental quality. Physical data obtained from measurements of over 270 work stations indicated the presence of cold temperatures, low light levels, reduced VDT screen contrast, glare, and distracting noises. The report provides the basic data that support the concerns expressed by Headquarters; namely, that field-station personnel perform their jobs under conditions likely to impair their effectiveness. Suggestions for improving conditions are given in a companion report by Rubin and Collins.
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 ...
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1?year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine ...
As coal becomes more and more important as a power plant fuel in this time of energy shortage and the combustion of high-sulfur coals that would impair air quality, efforts have been made to devise efficient processes to control sulfur dioxide emission. Besides desulfurization before combustion, flue gas desulfurization is considered the most promising method that could also be applicable to all other fossil fuels. In this article, the flue gas desulfurization processes are briefly reviewed, and processes with highest use and with high potential for future use are compared from technical and economical points of view. In the selection of a desulfurization process, it is very important to consider the capacity of the plant, fuel type and fuel-to-sulfur ratio, availability and price of the reagent to be used, type, price, and market of side products, disposal problems of wastes, and environmental factors.
With the advent of subgenomic hepatitis C virus (HCV) replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate JFH-1, efficient replication of these HCV RNAs requires replication enhancing mutations (REMs), previously also called cell culture adaptive mutations. These mutations cluster primarily in the central region of non-structural protein 5A (NS5A), but may also reside in the NS3 helicase domain or at a distinct position in NS4B. Most efficient replication has been achieved by combining REMs residing in NS3 with distinct REMs located in NS4B or NS5A. However, in spite of efficient replication of HCV genomes containing such mutations, they do not support production of infectious virus particles. By using the genotype 1b isolate Con1, in this study we show that REMs interfere with HCV assembly. Strongest ...
Studies on the regulation of the enterocytic differentiation of the human colon cancer cell line HT-29, which is differentiated in the absence (Glc"-) but not in the presence of glucose (Glc"+), have recently shown that the post-translational processing of sucrase-isomaltase and particularly its glycosylation vary as a function of cell differentiation. Other studies indicate that in undifferentiated HT-29 Glc"+ cells there is an accumulation of UDP-N-acetylhexosamine, which is involved in the glycosylation process. The purpose of the present work is to investigate whether an overall alteration of protein glycosylation is associated with the inability of HT-29 cells to differentiate. At least three alterations are detected: (i) after a 10-min pulse, the incorporation of D-[2-"3H]mannose in undifferentiated cells is severely reduced, compared to differentiated cells. (ii) After a 24-h period of labeling with D-[2-"3H]mannose, undifferentiated cells accumulate more than 60% of the ...
The performance of the Magma Power Company's reinjection well No. 46-7 at East Mesa has been examined. Water was cooled to 100/sup 0/F(+-) to simulate total heat extraction and then tested using membrane filter flow procedures. The cooled water contains particles which are in the high colloid size range, and formation impairment by these particles is unlikely. There is evidence that acid soluble corrosion products and calcium compounds constitute about two thirds of the particulates, and that the acid insoluble residue contains precipitated silica, insoluble corrosion products, and possibly formation fines carried in the produced water. Under stabilized conditions, the suspended solids content of the water is less than 2 parts per million. However, during the frequent production well start ups, a higher concentration of suspended solids is carried in the produced water and into the injection well, conceivably augmenting fill in the injector. But most ...
Functional magnetic resonance imaging (fMRI) in young children may provide information about the development of the visual cortex, and may have predictive value for later visual performance. The purpose of this study was to evaluate the usefulness of fMRI for examining cerebral processing of vision in very young infants and in infants with brain damage. We examined 15 preterm infants, 12 children suspected of having a cerebral visual impairment and 10 children with a normal visual system, all of whom were either spontaneously asleep or sedated with chloral hydrate. Cortical response to stroboscopic light stimulation could be demonstrated in all technically acceptable data sets from children with a post-menstrual age (PMA) of > 41 weeks, but not in younger infants. Children < 60 weeks PMA showed either a blood oxygenation level-dependent (BOLD) signal increase or decrease, while all older children showed a signal decrease. The activated cortical volumes showed ...
BackgroundNatural disasters result in significant numbers of disabling impairments. Paradoxically, however, the traditional health system response to natural disasters largely neglects health-related rehabilitation as a strategic intervention.ObjectivesTo examine the role of health-related rehabilitation in natural disaster relief along three lines of inquiry: (1) epidemiology of injury and disability, (2) impact on health and rehabilitation systems, and (3) the assessment and measurement of disability.DesignQualitative literature review and secondary data analysis.ResultsAbsolute numbers of injuries as well as injury to death ratios in natural disasters have increased significantly over the last 40 years. Major impairments requiring health-related rehabilitation include amputations, traumatic brain injuries, spinal cord injuries (SCI), and long bone fractures. Studies show that persons with pre-existing disabilities are more likely to die in a ...
Background. Metabolic disturbances such as anoxia and hypoglycaemia are important in causing maldevelopment of the neonatal brain. While there have been some pathology studies of the effects of neonatal hypoglycaemia on brain development, reports of MRI findings in such infants have been rare. Objectives. To describe the MRI findings in neurologically handicapped children who had suffered from neonatal hypoglycaemia and to evaluate the relationship between the neurological impairment and neonatal hypoglycaemia. Materials and methods. We retrospectively evaluated the MRI findings in eight full-term infants with neonatal symptomatic hypoglycaemia who later exhibited neurological handicap. The age at which the MRI scans were obtained ranged from 9 months to 8 years 10 months (mean 4 years 1 month, median 4 years). Results. The most striking findings were prolonged T1 weighting and T2 weighting in the parieto-occipital periventricular deep white matter in six patients, ...
Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized seizures was attenuated, seizure scores were ...
Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected ...
PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying patients at risk of liver-related complications. Findings from studies investigating the validity of the Model for End-Stage Liver Disease (MELD) score in HIV-infected liver transplant candidates are conflicting. Two large studies of HIV/hepatitis C virus (HCV) coinfected patients have shown that plasma levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models with the MELD or the Child-Pugh-Turcotte scores. SUMMARY: Although the data are ...
The definition of episodic memory includes the concept of mental time travel: the ability to re-experience a previously experienced trajectory through continuous dimensions of space and time, and to recall specific events or stimuli along this trajectory. Lesions of the hippocampus and entorhinal cortex impair human episodic memory function and impair rat performance in tasks that could be solved by retrieval of trajectories. Recent physiological data suggests a novel model for encoding and retrieval of trajectories, and for associating specific stimuli with specific positions along the trajectory. During encoding in the model, external input drives the activity of head direction cells. Entorhinal grid cells integrate the head direction input to update an internal representation of location, and drive hippocampal place cells. Trajectories are encoded by Hebbian modification of excitatory synaptic connections between hippocampal place cells and ...
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) and AbcA (6-fold). ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through regulating cell autophagy by ...
Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human ...
Purpose: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. Methods and Materials: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. Results: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue of Group 2 patients showed similar pattern levels (high and low) as that of superoxide dismutase/catalase. The association of cyclooxygenase-2 and p53 with various ...
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS-4 and low-dose honokiol significantly ...
Purpose: Previous data suggest that the PKC? catalytic V5 (PKC?-V5) heptapeptide (HEPT) (FEQFLDI) binds HSP27 and blocks HSP27-mediated radio- or chemoresistance. Here we investigated further the in vivo function of the PKC?-V5 HEPT. Methods and Materials: Labeling of HEPT with Cy5.5 or fluorescein isothiocyanate was performed to evaluate in vitro or in vivo distribution of HEPT. A clonogenic survival assay, flow cytometry, and Western blotting of cleaved caspase-3 were performed to determine in vitro sensitization effects of HEPT plus ionizing radiation (IR) versus IR alone or those of HEPT plus cisplatin(Cis) versus Cis alone. A nude mouse xenografting system was also applied to detect in vivo sensitizing effects of HEPT. Results: HEPT efficiently bound to HSP27 and showed sensitization after combined treatment with IR versus treatment with Cis alone in NCI-H1299 lung carcinoma cells, with higher HSP27 expression, which was similar to that of combined treatment with IR or with Cis ...
The COOH-terminus of telomerase reverse transcriptase (hTERT) has been shown to participatein the nuclear translocation of TERT. Here, we constructed plasmids expressing the COOH-terminal M(r) 27,000 polypeptide of hTERT (hTERTC27) withthe telomerase RNA-binding domains and the reverse transcriptase domains deleted. We showed that ectopic overexpression of this polypeptide caused a defect in telomere maintenance in hTERT-positive HeLa cells, which led to senescence-like growth arrest and apoptosis. The hTERTC27 appears to work by inducing telomere dysfunction, exemplified by significantly increased anaphase chromosome end-to-end fusion events in transfected cells. Significantly, it had no effect on the cellular telomerase enzymatic activity or telomere length. The in vivo effect was further demonstrated as HeLa cells stably expressing hTERTC27 have significantly lower growth rate and reduced tumorigenicity in nude mice xenografts. Results from this study revealed ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd{sup 2+} and Cu{sup 2+} concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase in AvPCS expression may contribute ...
To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd"2"+ and Cu"2"+ concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase in AvPCS expression may contribute to ...
Apoptosis, or programmed cell death (PCD), is a fundamental process that protects organismal integrity. In earlier work, we demonstrated that over-expression of either of two anti-apoptotic members of the BCL-2 family (BCL-2 or BCL-X L could elevate the frequency of radiation-induced mutations at the autosomal TK1 locus in human TK6 lymphoblasts that express wild-type TP53. Ectopic expression of BCL-X L also elevated the frequencies of double-strand break-induced gene conversion. The purpose of this study is to determine if BCL-2 family proteins promote radiation mutagenesis indirectly through their suppression of PCD, or whether the 'pro-mutagenic' function of these proteins can be separated from their anti-apoptotic function. We developed stable transfectants of TK6 cells that express a mutated form of BCL-X L with a single amino acid substitution in the BH1 domain that is known to interfere with the ability to suppress PCD (BCL-X L gly159ala). We also developed ...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor ...
Haemangiomas usually develop within the first few weeks of life, most regressing spontaneously before the age of 7 years. Some may ulcerate or compromise a vital function, in which case systemic corticosteroids, surgery or radiotherapy may be helpful. All of these treatment modalities are associated with significant morbidity. Treatment with the 585 nm flashlamp pulsed dye laser is safe and effective in the management of superficial vascular malformations. We report seven patients, under 12 months of age, who presented with proliferative haemangiomas, causing functional impairment. Ulcerated lesions were present in four patients. The patients were treated with the 585 nm pulsed dye laser (fluences 7.0-9.25 J/cm2), at intervals of 4-8 weeks. All of the lesions showed a significant reduction in size, together with improvement in the colour and integrity of the overlying skin. Treatment with the 585 nm pulsed dye laser should be considered in the management of infants ...
Delusional beliefs are characteristic of psychosis and, of the delusions, the paranoid delusion is the single most common type associated with psychosis. The many years of research focused on neurocognition in schizophrenia, using standardized neurocognitive tests, have failed to find conclusive cognitive deficits in relation to positive symptoms. However, UK-based psychological research has identified sociocognitive anomalies in relation to paranoid thinking in the form of theory of mind (ToM), causal reasoning and threat-related processing anomalies. Drawing from recent neuroscientific research on the default mode network, this paper asserts that the common theme running through the psychological tests that are sensitive to the cognitive impairment of paranoia is the need to cognitively project the self through time, referred to as mental time travel. Such an understanding of the cognitive roots of paranoid ideation provides a synthesis between psychological and ...
The iron hormone hepcidin is inhibited by matriptase-2, a liver serine-protease encoded by TMPRSS6 gene. Cleaving the BMP-coreceptor hemojuvelin, matriptase-2 impairs the BMP/SMAD signaling pathway, downregulates hepcidin and facilitates iron absorption. TMPRSS6 inactivation causes iron-deficiency-anemia refractory to iron administration both in humans and mice. Genome wide association studies have shown that the SNP rs855791, which causes the matriptase-2 V736A amino acid substitution, is associated with variations of serum iron, transferrin saturation, hemoglobin and erythrocyte traits. Here we show that in vitro matriptase-2 736(A) inhibits hepcidin more efficiently than 736(V). Moreover, in a genotyped population, after exclusion of samples with iron deficiency and inflammation, hepcidin, hepcidin/transferrin saturation and hepcidin/ferritin ratios were significantly lower and iron parameters were consistently higher in homozygotes 736(A) than in 736(V). Our ...
The non-blast furnace coke produced in the shaft ovens of the Angarsk Semi-coking Plant is used principally in gas generator ovens and partially as a carbonaceous reducing agent in the ferroalloy process. The sulfur content of this coke is not limited by the standards documents, but it is significant, especially in the production of process gases. In a number of recent years the sulfur removal system of the gasification divisions have been experiencing difficulties, not achieving the assigned gas purification parameters, with a resulting H/sub 2/S concentration in the purified gas of 300-700 mg/m/sup 3/ as compared to the standard of 50. Realizing that in the gasification practically all the organic matter of the coke, including the sulfur, enters the gas, the impairment in the quality of the sulfur removal is related to the increase in the sulfur content of the coke. Thus, an analysis of the results was conducted for the determination of the sulfur content of the ...
For the interests of national security, many scientists who work in the field of nuclear forensic analysis have carried out extensive work in the past on the detection of radioactive material and attributions study, developed a series of scientific and technical means to trace and detect illicit circulation of nuclear materials used to weapons and other radioactive materials which impair public security. All these questions relate to physical, chemical, biological attribution of materials. The nuclear forensic analysis has already become a special, up-to-date sphere of learning. The goal of the study of nuclear forensics is to prevent terrorists from acquiring not only nuclear weapons but also mate- rials that can be used to make such weapons, including radioactive materials for nuclear power plants, and medical radioisotope to and provide us as many clues of environmental links as possible that could help us trace the smuggling path, to answer the following ...
We studied regional myocardial perfusion by scintigraphic computer-assisted analysis of initial distribution, washout rates, and residual activity of "1"3"3Xe injected into the left coronary artery of four patients with normal arteriograms and 14 patients with coronary stenosis. At rest, residual activity in poststenotic regions was always greater than in control regions, but initial washout rates were not slower. During angina, following xenon injections, the amount of indicator distributed to the poststenotic regions was markedly reduced; the increase of the initial washout rates was smaller than in control regions relative to rest, and residual activity was higher. Initial washout rates did not differ as much as from those of normal myocardium because in severe ischemia too little indicator is deposited initially in these regions to produce a change of any magnitude. Indeed, when angina was induced immediately after the xenon injection, poststenotic washout rates became much slower ...
The build-up of frost on unit cooler surfaces, if not periodically cleared, will eventually cause impairment of the unit's performance, eventually rendering it useless. Thus it is necessary, in spaces below freezing, to provide an external supply of heat to warm the unit sufficiently to melt the frost and remove it. In large central-plant-type systems the most common method employed for supplying heat is from the high-pressure side of the refrigeration system, referred to as hot gas defrost. Although the heat thus captured for use in melting frost would otherwise be rejected external to the system, the defrosting process is not free of cost. There are significant losses associated with the process the magnitude of which have not heretofore been fully identified. This paper looks at the heat and mass transfer and fluid flow mechanisms involved in the hot gas defrost process in large commercial freezers. It suggests some mathematical models for analysis of ...
Severe damage to the pelvic viscera is a complication of irradiation therapy that, unfortunately, cannot always be avoided. Resulting rectal and rectocolonic strictures, rectovaginal fistulas, and shortening and stenosis of the vagina present very difficult problems that frequently require a colostomy for relief and may permanently impair sexual function. The authors present a new approach to correction of these unfortunate lesions based on the use of proximal nonirradiated colon which serves as a vascular pedicle graft to correct the defect without a complicated and massive resection. Twenty-two such operations have been done with 19 satisfactory to excellent results and two total failures (one death from small bowel complications). All patterns and combinations of irradiation injury have been found amenable to this technique of repair. These have included both web and linear strictures with and without fistulas. In half of the patients, it was possible to make ...
The world fusion program has advanced to the stage where it is appropriate to construct a number of devices for the purpose of burning DT fuel. In these next-generation experiments, the expected flux and fluence of 14 MeV neutrons and associated gamma rays will pose a significant challenge to the operation and diagnostics of the fusion device. Radiation effects include structural damage to materials such as vacuum windows and seals, modifications to electrical properties such as electrical conductivity and dielectric strength and impaired optical properties such as reduced transparency and luminescence of windows and fiber optics during irradiation. In preparation for construction and operation of these new facilities, the fusion diagnostics community needs to work with materials scientists to develop a better understanding of radiation effects, and to undertake a testing program aimed at developing workable solutions for this multi-faceted problem. A unique ...
Seizures are a frequent sequela of impaired brain development and can be expected to affect more children with radiation-related brain damage than children without such damage. This report deals with the incidence and type of seizures among survivors prenatally exposed to the atomic bombing of Hiroshima and Nagasaki, and their association with specific stages of prenatal development at the time of irradiation. Fetal radiation dose was assumed to be equal to the dose to the maternal uterus. Seizures here include all references in the clinical record to seizure, epilepsy, or convulsion. Histories of seizures were obtained at biennial routine clinical examinations starting at about the age of 2 years. These clinical records were used to classify seizures as febrile or unprovoked (without precipitating cause). No seizures were ascertained among subjects exposed 0-7 weeks after fertilization at doses higher than 0.10 Gy. The incidence of seizures was highest with ...
Limited field trial results of a heating oil additive package developed to minimize unscheduled maintenance indicate that it achieves its goal of keeping heating oil systems cleaner. The multifunctional additive package was developed to provide improved fuel oxidation stability, improved corrosion protection, and dispersency. This combination of performance benefits was chosen because we believed it would retard the formation of sludge, as well as allow sludge already present to be carried through the system without fouling the fuel system components (dispersency should keep sludge particles small so they pass through the filtering system). Since many unscheduled maintenance calls are linked to fouling of the fuel filtering system, the overall goal of this technology is to reduce these maintenance calls. Photographic evidence shows that the additive package not only reduces the amount of sludge formed, but even removes existing sludge from filters and pump strainers. This ...
This study aimed to reveal that severe disturbance of attachment relationship with primary care-giver can affect functional and anatomical brain development by measuring cerebral perfusion on "9"9"mTc-ECD brain SPECT and correlative MRI. We included 18 children aged 31 to 76 months who met the diagnostic criteria of RAD as defined in DSM-IV and ICD-10 and SSP and CARS. "9"9"mTc-ECD SPECT was performed using CERASPECT. MRI was performed in all patients. SPECT data were visually assessed. 15 of 18 children had abnormal perfusion on SPECT, revealing decreased perfusion of Lt.thalamus (7/15) and Rt.thalamus (3/15), and bilateral thalami (5/15). Perfusion of basal ganglia was decreased in 8 children. Decreased perfusion of Lt. parietal area was seen in 2. Whereas, all patients had normal MR findings. Perfusion abnormalities involving thalamus, BG in most children with RAD were found in this study. These results suggest that brain development of infant could be impeded by severe pathologic ...
In the Assel'skiy and Sakmarskiy time of the lower Permian epoch, on the territory of the modern Dnieper and Donets, and Pripyatskiy Basins, there was a gulf which stretched in a northwest direction. The latter connected to the open sea in the east through the CisDonets trough. Transverse tectonic elevations divided the gulf into 5 semi-isolated reservoirs. In the Assel'skiy time, in the period of carbonate sedimentation, the development of algae, crinoids, corals and other organisms occurred. They created reef, bioherm and biostroma reconstructions. The most favorable sections for their settlement were the coastal zones of the gulf, consedimentation positive structures and transverse tectonic elevations. It is assumed that the formation of reefs, bioherms and biostromas, on the one hand, and sedimentation of evaporites on the other hand, are interrelated processes. The first after the next marine transgression during their growth was a greater ...
There is increasing use of radiofrequency radiation (RFR) in industry for communications, welding, security, radio, medicine, navigation etc. It has been recognised for some years that RFR may interact with cardiac pacemakers and steps have been taken to prevent this interference. It is less well recognised that other metallic implants may also act as antennas in an RFR field and possibly cause adverse health effects by heating local tissues. There are a large and increasing number of implants having metal components which may be found in RFR workers. These implants include artificial joints, rods and plates used in orthopaedics, rings in heart valves, wires in sutures, bionic ears, subcutaneous infusion systems and (external) transdermal drug delivery patches"1. The physician concerned with job placement of such persons requires information on the likelihood of an implant interacting with RFR so as to impair health. The following outlines the approach developed in ...
Therapeutic hypothermia is a promising method for controlling intracranial pressure (ICP) in severely brain-injured patients. However, clinical data regarding the effect of brain hypothermia on overall outcome of these patients is limited. This may be because there are specific pitfalls associated with the clinical management of induced hypothermia in patients with severe traumatic brain injury (TBI). These pitfalls may be avoided by preventing specific risk factors when cooling is induced and with rewarming. However, these risk factors have not been well systematically discussed in the literature. In this paper, three categories of clinical issues regarding the management of brain hypothermia are discussed: (1) stress-induced secondary brain injury mechanisms; (2) technical aspects of intensive care unit (ICU) cooling management; and (3) rewarming rates and methods. For patients with a Glasgow Coma Scale (GCS) score of less than 8, management of stress-induced insulin-resistant ...
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...
Despite successful reduction of the general lead exposure, this heavy metal is still a matter of public concern due to the fact that associations with intellectual impairment or delayed puberty are found to correlate with very low lead blood concentrations. Lead in tap water is still an important contribution to lead exposure which may cause health risk for infants. Therefore, lead pipes should be completely sanitated by exchange against pipes made from more healthy materials. (orig.) [German] Trotz erfolgreicher Reduktion der allgemeinen Belastung ist Blei auch heute noch umweltmedizinisch relevant, weil es moeglicherweise bei niedrigeren als bisher angenommenen Belastungen gesundheitlich nachteilige Wirkungen, insbesondere waehrend der fruehkindlichen Entwicklung des Nervensystems, ausloest. Insbesondere Blei aus bleiernen Trinkwasserleitungen ist eine Belastung, die fuer Saeuglinge und Kleinkinder nach wie vor ein gesundheitliches Risiko darstellen kann. Solche ...
To determine the diagnostic accuracy of iofetamine hydrochloride I 123 (IMP) with single photon emission computed tomography in Alzheimer's disease, we studied 58 patients with AD and 15 age-matched healthy control subjects. We used a qualitative method to assess regional IMP uptake in the entire brain and to rate image data sets as normal or abnormal without knowledge of subjects'clinical classification. The sensitivity and specificity of IMP with single photon emission computed tomography in AD were 88% and 87%, respectively. In 15 patients with mild cognitive deficits (Blessed Dementia Scale score, less than or equal to 10), sensitivity was 80%. With the use of a semiquantitative measure of regional cortical IMP uptake, the parietal lobes were the most functionally impaired in AD and the most strongly associated with the patients' Blessed Dementia Scale scores. These results indicated that IMP with single photon emission computed ...
In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca/sup 2 +/-ATPase activity and /sup 45/Ca uptake were determined in brain P/sub 2/ fraction. Toxaphene inhibited both Ca/sup 2 +/-ATPase activity and /sup 45/Ca/sup 2 +/ uptake and the inhibition was dose dependent. Both substrate and Ca/sup 2 +/ activation kinetics of Ca/sup 2 +/-ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca/sup 2 +/-ATPase activity and Ca/sup 2 +/ uptake were restored to normal level by exogenously added calmodulin which increased both velocity and affinity. The inhibition of Ca/sup 2 +/-ATPase activity and Ca/sup 2 +/ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms ...
In vivo effects of toxaphene on calcium pump activity in rat brain synaptosomes was studied. Male Sprague-Dawley rats were dosed with toxaphene at 0,25,50, and 100 mg/kg/day for 3 days and sacrificed 24 h after last dose. Ca"2"+-ATPase activity and "4"5Ca uptake were determined in brain P_2 fraction. Toxaphene inhibited both Ca"2"+-ATPase activity and "4"5Ca"2"+ uptake and the inhibition was dose dependent. Both substrate and Ca"2"+ activation kinetics of Ca"2"+-ATPase indicated non-competitive type of inhibition as evidenced by decreased catalytic velocity but not enzyme-substrate affinity. The inhibited Ca"2"+-ATPase activity and Ca"2"+ uptake were restored to normal level by exogenously added calmodulin which increased both velocity and affinity. The inhibition of Ca"2"+-ATPase activity and Ca"2"+ uptake and restoration by calmodulin suggests that toxaphene may impair active calcium transport mechanisms by decreasing regulator protein calmodulin levels.
Describes investigations into flow density, angle of repose, coefficients of friction and adhesion using poor quality anthracite culm (from the 50-letie Ukrainy mine) and anthracite slurry with a high ash content (from the Tsentral'naya and Partizanskaya mines) on samples of varying moisture content (2-22%). The results show that flow properties are impaired when anthracite has a moisture content of 8.5 to 9.5%; when these anthracites are used in electric power plants they should be stored in bunkers with walls with a slope of greater than 70 degrees (or dried) to prevent sticking. Results of investigations into internal and external friction, adhesion and cohesion varied for the different samples, but the highest coefficient of internal friction was found with concrete where it increases continuously with moisture content. With rubber, PVC, St. 3 steel and stainless steel, the friction coefficient increases with moisture content at first, then gradually ...
Fitness, (biometric measurements, reproduction) and behaviour that are ecologically relevant biomarkers in assessing the quality of estuarine sediments were studied by comparing the responses of the polychaete worm Nereis diversicolor - a key species in estuaries - along a pollution gradient. Intersite differences were shown for all the measured parameters: size-weight relationships, energy reserves as glycogen and lipids, sexual maturation patterns, total number of oocytes per female, total and relative fecundity, burrowing behaviour. The physiological and behavioural status of N. diversicolor was consistently disturbed in the larger, most contaminated estuaries (Loire and Seine, Fr.) compared to reference sites (Bay of Bourgneuf, Goyen estuary, Fr.). Many classes of potentially toxic chemicals present in these estuaries most likely contribute to these impairments but food availability may act as a confounding factor, interfering with the potential impact of ...
Coastal zones are among the most productive and vulnerable areas on the planet. An example of impact on these fragile environments was shown in the case of the Sea Empress oil tanker, which ran aground in the Bristol Channel in 1996, spilling 72,000 tonnes of Forties crude oil. The objective was to investigate the sub-lethal cellular pathology and tissue hydrocarbon contamination in marine mussel populations, 4 months after the initial spill, using the neutral red retention (NRR) assay for lysosomal stability in blood cells. NRR was reduced in mussels, and indicative of cell injury, from the two sites closest to the spill in comparison with more distant and reference sites. Lysosomal stability was inversely correlated with polycyclic aromatic hydrocarbon concentrations in mussel tissues. Reduced lysosomal stability has previously been shown to contribute to impaired immunocompetence and to autophagic loss of body tissues. The use of this type of technique is ...
The contents of immunoreactive somatostatin (IR-SRIF) and ..beta..-endorphin (IR-..beta..-EP) in 12 brain regions were examined in rats exposed neonatally to propylthiouracil (PTU) through the mother's milk. Since the dose of PTU used in this study is lower than the usual dose employed to induce hypothyroidism, a milder form of neonatal hypothyroidism resulted. This conclusion is supported by the only mild subnormal growth of rats to adulthood and serum T/sub 4/ and T/sub 3/ concentrations in the normal range. Adult rats treated with PTU neonatally had significantly higher IR-SRIF contents in several brain regions compared to controls, whereas IR-..beta..-EP levels were not significantly different in most regions. The results indicate that even mild hypothyroidism during early postnatal development causes permanent impairment of brain function, which manifests itself in part by an altered brain content of IR-SRIF.
A high sensitivity (titer 60-150,000) radioimmunoassay for arginine vasopressin (AVP) has been developed using synthetic AVP as antigen and standard. The specificity of the antiserum has been characterized in detail by measuring the relative binding affinities of 29 analogs and fragments of AVP. In general, single amino acid substitution or deletion in the AVP molecule caused a reduction in binding to the antiserum; binding was further impaired for analogs which had multiple substitutions. ''Ring'' and ''tail'' fragments of the neurohypophysial hormones did not bind to the antiserum, and the only analog which the antiserum could not differentiate from AVP was deamino-AVP. More specifically, the antiserum exhibited the following properties: position 1, no requirement for a position charge at "1/_2 Cys; positions 2 and 3, requirements for #pi#-#pi# interacting pair of aromatic side chains and for Tyr at position 2; position 4, requirement for Gln (>Thr > Val); ...
The volume of cortical activation as detected by functional magnetic resonance imaging (fMRI) in the visual cortex has previously been shown to be reduced following optic neuritis (ON). In order to understand the cause of this change, we studied the cortical activation, both the size of the activated area and the signal change following ON, and compared the results with results of neuroophthalmological testing. We studied nine patients with previous acute ON and 10 healthy persons served as controls using fMRI with visual stimulation. In addition to a reduced activated volume, patients showed a reduced blood oxygenation level dependent (BOLD) signal increase and a greater asymmetry in the visual cortex, compared with controls. The volume of visual cortical activation was significantly correlated to the result of the contrast sensitivity test. The BOLD signal increase correlated significantly to both the results of the contrast sensitivity test and to the Snellen visual acuity. Our ...
Femoral head vitality before, during and at various intervals from the operation was determined by tetracycline labeling and/or _9_9 sp (m)Tc-MDP scintimetry. In a three-year follow-up, healing prognosis could be determined by scintimetry 3 weeks from operation; deficient femoral head vitality predicting healing complications and retained vitality predicting uncomplicated healing. A comparison between pre- and postoperative scintimetry indicated that further impairment of the femoral head vitality could be caused by the operative procedure, and as tetracycline labeling prior to and after fracture reduction in 370 fractures proved equivalent, it was concluded that the procedure of osteosynthesis probably was responsible for capsular vessel injury, using a four-flanged nail. The four-flanged nail was compared with a low-traumatic method of osteosynthesis, two hook-pins, in a prospective randomized 14 month study, and the postoperative femoral head vitality was ...
During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs. To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology. We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction. Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam. Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease ...
Fourteen surgical patients with non-hepatobiliary diseases were studied with "9"9Tc"m EHIDA imaging to evaluate the effect of total parenteral nutrition (TPN) on the hepatobiliary function. The duration of TPN ranged from 6 to 56 days; for 10 of the 14 patients it was between 6 to 10 days. The results showed that: (1) 11 of 14 patients had abnormal scintigraphic features. The most prominent findings were delayed liver excretion and prolonged blood clearance time. This fact suggests that not only the rate of excretion of the bile from the liver is decreased but the uptake ability of the hepatocyte is also impaired. (2) The effect of TPN on liver function is reversible. The authors conclude that in order to prevent irreversible damage of hepatobiliary function caused by TPN, the duration of TPN should not be too long and oral intake of nutrients should be resumed as soon as possible. (author). 9 refs, 3 figs, 3 tabs.
Premature fusion of multiple cranial sutures has been associated with increased intracranial pressure and the potential for mental impairment. Isolated craniosynostosis, however, is considered a benign condition primarily reconstructed for aesthetic purposes. A comparative analysis, to assess the differences between pre- and post operatory cerebral perfusion of patients who underwent surgery for simple cranisynostosis, was performed using single positron emission computed tomography ''SPECT'' Images. Cerebral blood flow studies were performed using "9"9"mTc-HMPAO SPECT in children with simple cranisynotoses. The subjects were 8 children with craniosynostosis (age, 2 months-9 years). Preoperative revealed regional hypovascularity in the cerebral hemisphere in 5 cases (62%). In 6 patients the cerebral blood flow normalized or increased after craniofacial reconstruction. We demonstrated the presence of regional hypovascularity in the cerebral hemisphere of simple ...
The purpose was to compare the findings of multi-detector computed tomography (MDCT) in prosthetic valve disorders using the operative findings as a gold standard. In a 3-year period, we prospectively enrolled 25 patients with 31 prosthetic heart valves. MDCT and transthoracic echocardiography (TTE) were done to evaluate pannus formation, prosthetic valve dysfunction, suture loosening (paravalvular leak) and pseudoaneurysm formation. Patients indicated for surgery received an operation within 1 week. The MDCT findings were compared with the operative findings. One patient with a Bjoerk-Shiley valve could not be evaluated by MDCT due to a severe beam-hardening artifact; thus, the exclusion rate for MDCT was 3.2% (1/31). Prosthetic valve disorders were suspected in 12 patients by either MDCT or TTE. Six patients received an operation that included three redo aortic valve replacements, two redo mitral replacements and one Amplatzer ductal occluder occlusion of a mitral paravalvular leak. ...
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 dysentery. ...
Small bowel obstructions can be distinguished into more simple and closed loop obstructions. The latter is a more severe condition which is often complicated by strangulation with vascular impairment, edema and intramural and mesenteric hemorrhage. Consequent arterial insufficiency rapidly leads to ischemia, infarction and necrosis. The radiologist plays a role in the early recognition of the closed loop obstruction and of any sign of strangulation. The role of CT in the diagnosis and workup of patients with suspected intestinal occlusion has been analyzed in the literature with reported 63% sensitivity, 78% specificity and 66% accuracy. CT is also capable of revealing the causes of occlusion in 73-95% of cases. The above CT signs allow to identify closed loop obstruction and also small bowel strangulation, thus supplying a valuable contribution to diagnosis and accurate preoperative evaluation. The conclusion is that CT can accurately demonstrate the presence of ...
N-ethyl-N-nitrosourea (ENU) mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as Sp(xG). Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the Sp(xG) was confined to a region between D1MIT415 and D1MIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that Sp(xG) carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain (HD) DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired the transactivation ...
Systemic sclerosis is an autoimmune connective tissue disorder characterized by a widespread microangiopathy, autoimmunity and fibrosis of the skin and of various internal organs. Microangiopathy is characterized by a reduced capillary density and an irregular chaotic architecture that lead to chronic tissue hypoxia. Despite the hypoxic conditions, there is no evidence for a sufficient compensative angiogenesis in SSc. Furthermore, vasculogenesis is also impaired. An imbalance between angiogenic and angiostatic factors might explain the pathogenetic mechanisms of SSc vasculopathy. As far as angiogenic factors are concerned, within the most important are vascular endothelial growth factor (VEGF) and its receptors, platelet derived growth factor (PDGF), transforming growth factor beta (TGF-?), fibroblast growth factor -2 (FGF-2), angiopoietin 1 (Ang-1), stromal cell-derived factor 1 (SDF-1/CXCL12), endothelin-1 (ET-1), monocyte chemoattractant protein -1 (MCP-1), ...
The aqueous fraction (AF) of an ethanolic extract from Chrysanthemum indicum was evaluated for analgesic activity in mice using chemical and thermal models of nociception. Given orally, AF at doses of 300 and 600 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the pentobarbital sodium-induced sleeping time test and the open-field test, AF neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed analgesic activity was unlikely due to sedation or motor abnormality. In a measurement of core body temperature, AF did not affect temperature within 80 min. Moreover, the effective dose (600 mg/kg) also showed no toxicity within 7 days. These results suggested further that AF produced analgesic activity possibly ...
Childhood anxiety is impairing and associated with later emotional disorders. Studying risk factors for child anxiety may allow earlier identification of at-risk children for prevention efforts. This study applied an ecological risk model to address how early childhood anxiety symptoms, child temperament, maternal anxiety and depression symptoms, violence exposure, and sociodemographic risk factors predict school-aged anxiety symptoms. This longitudinal, prospective study was conducted in a representative birth cohort (n = 1109). Structural equation modeling was used to examine hypothesized associations between risk factors measured in toddlerhood/preschool (age = 3.0 years) and anxiety symptoms measured in kindergarten (age = 6.0 years) and second grade (age = 8.0 years). Early child risk factors (anxiety symptoms and temperament) emerged as the most robust predictor for both parent-and child-reported anxiety outcomes and mediated the effects of maternal and ...
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 traits studied suggested that the best ...
Objectives1. To identify with older people the problems which they encounter in finding their way about public building/spaces.~%~2. To produce ideas, in consultation with older people, for an information/navigation aid that might facilitate their use and enjoyment of public buildings/spaces, notably hospitals, large shops, railway stations, airports.~%~3. To develop an emulation model of the information/navigation aid~%~4. To monitor use of the model by older people~%~5. To identify further research~%~6. [continued...]DescriptionThe growth in the number of older people offers scope for the development of customised information/navigation aids to help them to find their way around complex public spaces. New technology however is unlikely to be taken up by older people unless it is acceptable to them. The research will involve engineers in designing, testing and modifying a model of such an aid in conjunction with a sample of older people.~%~Older people, in particular those with ...
A study on brain CT was made in 20 cases of typical endemic cretinism and 15 cases of normal persons. These patients from severely iodine deficient area were diagnosed as neurological endemic cretinism characterized by severe mental retardation with impairment of hearing, speech, neuromotor, etc. to varying degrees. The brain CT showed that there were many and deep depressions in cerebral cortex, especially in frontal and parietal lobes of some cretins, the lateral ventricle system was dilated, particularly in posterior part of it, and the interhemisphere fissure, lateral fissure and subarachnoid cisterns were also expanded. The CT value of cortex was higher and white matter was lower than that of normal persons. In some severe cases, the two hemispheres of brain were not the same in size. These findings above indicated that these endemic cretins had a severe retardation of brain development including cerebral cortex and white matter. In addition, some abnormal ...
CT is the most accurate method to detect pulmonary emphysema in vivo. They compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT using a density mask program, at two different cut-off levels (-850,-900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas ...
Identification of factors that determine individual patient risk for recurrence and progression in superficial papillary carcinoma of the bladder is a subject of extensive research as it would be a major outcome in patient management. It has been well recognized that traditional prognostic markers as tumor grade and stage are not accurate enough in predicting biological behavior. A large number of markers have been investigated as potential prognostic factors and relatively few can help in predicting outcome. Material and Methods: Forty-nine cases undergoing complete transurethral resection for primary superficial papillary transitional cell carcinoma were subjected to clinicopathologic evaluation as well as immunohistochemical staining for p53, bcl-2, cytokeratin 20 and Ki-67. The CAS-200 image analyzer was used to estimate the Ki-67 labeling index. Results: Recurrence was observed in 19 cases (38.8%) and progression in 7 cases (14.3%) with a median followup of 49 months (range 24-84 ...
We report a search for small RNAs (sRNAs) in the low-GC, gram-positive human pathogen Streptococcus pneumoniae. Based on bioinformatic analyses by Livny et al. (J. Livny, A. Brencic, S. Lory, and M. K. Waldor, Nucleic Acids Res. 34:3484-3493, 2006), we tested 40 candidates by Northern blotting and confirmed the expression of nine new and one previously reported (CcnA) sRNAs in strain D39. CcnA is one of five redundant sRNAs reported by Halfmann et al. (A. Halfmann, M. Kovacs, R. Hakenbeck, and R. Bruckner, Mol. Microbiol. 66:110-126, 2007) that are positively controlled by the CiaR response regulator. We characterized 3 of these 14 sRNAs: Spd-sr17 (144 nucleotides [nt]; decreased in stationary phase), Spd-sr37 (80 nt; strongly expressed in all growth phases), and CcnA (93 nt; induced by competence stimulatory peptide). Spd-sr17 and CcnA likely fold into structures containing single-stranded regions between hairpin structures, whereas Spd-sr37 forms a base-paired structure. Primer ...
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal ...
We have previously shown that avian reovirus (ARV) #sigma#A and #sigma#NS proteins possess dsRNA and ssRNA binding activity and suggested that there are two epitopes on #sigma#A (I and II) and three epitopes (A, B, and C) on #sigma#NS. To further define the location of epitopes on #sigma#A and #sigma#NS proteins and to further elucidate the biological functions of these epitopes by using monoclonal antibodies (MAbs) 62, 1F9, H1E1, and 4A123 against the ARV S1133 strain, the full-length and deletion fragments of S2 and S4 genes of ARV generated by polymerase chain reaction (PCR) were cloned into pET32 expression vectors and the fusion proteins were overexpressed in Escherichia coli BL21 strain. Epitope mapping using MAbs and E. coli-expressed deletion fragments of #sigma#A and #sigma#NS of the ARV S1133 strain, synthetic peptides, and the cross reactivity of MAbs to heterologous ARV strains demonstrated that epitope II on #sigma#A was located at amino acid residues ...
The three mammalian transforming growth factor (TGF)-? isoforms (TGF-?1, TGF-?2, and TGF-?3) differ in their putative roles in radiation-induced fibrosis in intestine and other organs. Furthermore, tissue specificity of TGF-? action may result from temporal or spatial changes in production and/or activation. The present study examined shifts in the cell types expressing TGF-? mRNA relative to TGF-? immunoreactivity and histopathological injury during radiation enteropathy development. A 4-cm loop of rat small intestine was locally exposed to 0, 12, or 21-Gy single doses of x-irradiation. Sham-irradiated and irradiated intestine were procured 2 and 26 weeks after irradiation. Cells expressing the TGF-?1, TGF-?2, or TGF-?3 transcripts were identified by in situ hybridization with digoxigenin-labeled riboprobes. Intestinal wall TGF-? immunoreactivity was measured using computerized image analysis, and structural radiation injury was assessed by quantitative histopathology. Normal ...
These studies were undertaken to assess the effects of increased galactose (v increased glucose) metabolism via the polyol pathway on vascular filtration function in the kidneys, eyes, nerves, and aorta. Quantitative radiolabeled tracer techniques were used to assess glomerular filtration rate (GFR) and regional tissue vascular clearance of plasma 131I-bovine serum albumin (BSA) in five groups of male Sprague-Dawley rats: nondiabetic controls, streptozotocin-diabetic rats, nondiabetic rats fed a 50% galactose diet, diabetic rats treated with sorbinil (an aldose reductase inhibitor), and galactose-fed rats treated with sorbinil. Sorbinil was added to the diet to provide a daily dose of approximately .2 mmol/kg body weight. After 2 months of diabetes or galactose ingestion, albumin clearance was increased twofold to fourfold in the eye (anterior uvea, choroid, and retina), sciatic nerve, aorta, and kidney; GFR was increased approximately twofold and urinary excretion of endogenous ...
Plasma nitriding is usually used for ferrous materials to improve their surface properties. Knowledge of the properties of thin surface layers is essential for designing engineering components with optimal wear performance. In our study, we investigated the microstructural, mechanical and tribological properties of plasma- and pulse plasma-nitrided AISI 4140 steel in comparison to hardened steel. The influence of nitriding case depth as well as the presence of a compound layer on its tribological behaviour was also examined. Plasma and pulse plasma nitriding were carried out using commercial nitriding processes. Nitrided samples were fully characterised, using metallographic, SEM microscopic, microhardness and profilometric techniques, before and after wear testing. Wear tests were performed on a pin-on-disc wear testing machine in which nitrided pins were mated to hardened ball bearing steel discs. The wear tests were carried out under dry conditions where hardened samples were used ...
The influence of high C martensite on the strength and impact behavior of C-Mn-Nb-Al steels has been determined for two distributions: films surrounding the ferrite grains and distinct colonies. In the former case, the impact behavior markedly deteriorated, this deterioration increasing with martensite level. The changes in impact behavior could be explained by regarding the films of martensite as being similar to the brittle grain boundary carbides that are present in ferrite-pearlite steels. These films readily crack, yet are always thick enough to produce a sufficient wide crack to render crack propagation easy. The critical event in fracture then becomes the ability to propagate the cracks through the grain boundaries. The greater the grain boundary coverage by these films, the easier this becomes and the worse is the impact behavior. When the martensite is present as colonies, again the impact performance is seriously impaired, but to a lesser extent than when ...
A factor produced by plerocercoids of the tapeworm Spirometra mansonoides is similar to human growth hormone (hGH) in that it stimulates body growth, binds to hGH receptors, cross-reacts with anti-hGH antibodies, and has lactogenic and insulin-like activities. The purpose of this study was to determine whether plerocercoid growth factor (PGF) is similar to hGH in expressing diabetogenic activity in the genetically obese (ob/ob) mouse. To determine an effective dose for use in the obese mice, the ability of daily injections of PGF to stimulate growth of phenotypically normal mice of the same strain was assessed in a 10-day weight gain assay. Injections of PGF stimulated a dose-dependent weight gain (r = 0.83) and 25 ng eq/day of PGF stimulated a response not significantly different from that produced by 100 micrograms of bovine growth hormone/day. Diabetogenicity was assessed using fasting blood glucose and glucose tolerance tests in obese mice that had been injected for 3 days with ...
Placental insufficiency, inducing hypoxia-ischaemia, is considered a major cause of neuronal injury and impaired post natal development. Placental insufficiency alters the metabolism of arachidonic acid and its oxidation products. Premature labour and low-birth-weight infants are associated with reduced intrauterine blood-flow and infections of the reproductive tract. Thyroidal activity is depressed in undernutrition (placental insufficiency). Premature infants require extra vitamin C for normal tyrosine metabolism (tyrosine is the thyroxine precursor). Among the symptoms indicating infantile cretinism, which appear during 3-5 months of age are: delayed union of skull bones, torpid behaviour, slow feeding, cyanosis during feeding, excessive sleepiness, enlarged tongue, umbilical herniation, flabby musculature, short stature and delayed development. These symptoms have all been described in low-birth-weight infants and sudden infant death syndrome victims by various ...
There is extensive evidence that exposure to asbestos causes pulmonary parenchyma fibrosis, pleural disease, and malignant neoplasm in asbestos-exposed workers. However, few data concerning brake-lining workers are available in the literature. In this study, we aimed to assess the long-term effects of chrysotile asbestos exposure on lung function and the risk of asbestos-related diseases in brake-lining workers. Seventy-four asbestos-exposed workers who processed brake-lining products and 12 unexposed office workers were offered pulmonary function tests (spirometry and transfer actor) in 1992 and 1999. In 1999, the mean duration of asbestos exposure was 0.00#+-#4.07 and 11.02#+-#4.81 years (7-31 years) in non smoking and smoking asbestos workers, respectively. Transfer factor (T_L, CO) and transfer coefficient (K_C_O) decline were significant in the 7-year follow-up in both smoking and non smoking asbestos workers. However, lung function indices of he control group, whom were all ...
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 (P< or =0.01) in the ...
Objective: To explore the feasibility of real-time monitoring exposure dose and image quality by using the data stored in the DICOM image archive of direct digital radiography system. Methods: Model TO. 16 was exposed, the current increased gradually from 0.5 to 125 mAs. The displayed number of model A( diameter 11.1 mm), D (diameter 4.0 mm) and J( diameter 0.7 mm) were recorded, and the detect factors (H_T) was also calculated. Images were sent to workstation before the end of DR examination. An automatic procedure was implemented to extract dose data and exposure parameters from the DICOM header file. Maximum, minimum and 3rd quartile values were preinstalled. Mean values exceeding the threshold trigger alarm signal to guide radiologist to explore the cause. Results: When the current of point A was less than 10 mAs and the current of point D and J were less than 16 mAs, the detect factor (H_T) increased with the rise of current. While point A located within 10-100 mAs, point D and J ...
To analyze the enhancement patterns and morphology of peripheral cholangiocar-cinomas (CCs), as seen on three-phase helical CT. Three-phase helical CT scans of 25 cases of 24 patients with pathologically-proven CCs were retrospectively reviewed. After intravenous administration of contrast media, scans of the hepatic arterial phase (HAP) were obtained at 30 seconds, of the portal venous phase (PVP) at 70 seconds, and of the delayed phase (DP) at 3 minutes. Linear, dense, marginal enhancement was seen in 17 CCs (68%), mainly on HAP images (64%) while thick, band-like, peripheral enhancement was seen in 18 (72%), on either PVP (52%) or DP (44%). Internal enhancement was observed in 23 CCs (92%) on PVP (68%) and/or DP (88%), and 19 CCs (76%) among them showed incomplete enhancement of stippled and/or septated patterns. Most (76%) were seen throughout all three phases to be hypoattenuating, as compared to the surrounding parenchyma. On HAP, wedge-shaped parenchymal enhancement was ...
Recently the association of a rare disease named ''nephrogenic systemic fibrosis'' (NSF) with the administration of gadolinium-containing contrast media, especially gadodiamide (Omniscan, GE-Healthcare), was described. NSF is a scleroderma-like disease characterised by widespread tissue fibrosis. Until now, NSF cases were observed only in patients with kidney disease. Almost all patients were suffering from chronic renal insufficiency, 90 % of them required renal replacement therapy. The true incidence of the disease is unknown. First retrospective analyses of selected collectives of patients with end-stage renal disease showed 2 - 5 % cases of NSF after administration of Gadolinium-containing contrast agents with an odds ratio of 20 - 50 in comparison to non-exposed controls. NSF is a serious adverse reaction, which may result in severe disabilities and even death. Therefore all radiologists applying gadolinium-based contrast agents should be ...
Mucociliary transport so critical in nasal, paranasal sinus, and middle ear physiology is impaired in chronic sinsusitis and otitis media by factors such as increased mucus viscoelasticity, decreased ciliary area, and primary or secondary ciliary immotility. We reviewed the pathophysiology of primary ciliary dyskinesia, otitis media with effusion, chronic sinusitis, and allergic rhinitis in terms of mucociliary transport. Subjects with primary ciliary dyskinesia may experience recurrent middle ear infection, chronic airway infection, predominantly lower-lobe bronchiectasis, male sterility, or situs inversus. Primary ciliary dyskinesia is sometimes difficult to diagnose in cases without situs inversus. Nasal nitric oxide concentration in such patients decreases, although why is unclear. Mutations may involve dynein arm intermediate chain 1 (DNAI1) or dynein arm heavy chain 5 (DNAH5). Mucociliary clearance decreases more in those with otitis media with effusion than ...
Patients suffering from depression frequently display hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the "control group" (C), "exercise group" (E), "dexamethasone group" (D) and the "dexamethasone plus exercise group" (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using ...
A Norwegian Research Program on Improved Oil Recovery (IOR) in North Sea reservoirs was launched in 1992. Microbial methods, applied in this context, is a part of this program. The scope, the methodological approach, and results from the three first years are presented. Water profile control, using biomass to block high permeable zones of a reservoir, has been investigated using nitrate-reducing bacteria in the injected sea water as plugging agents. Emphasis has been put on developing a process that does not have disadvantages secondary to the process itself, such as souring and impairment of the overall injectivity of the field. Data from continuous culture studies indicate that souring may successfully be mitigated by adding nitrite to the injected seawater. The morphology and size of generic-nitrate-reducing seawater bacteria have been investigated. Screening of growth-promoting nutrients has been carried out, and some sources were detected as favorable. ...
Objectives: We have previously shown that chronic exposure to ambient fine particulate matter (less than 2.5 ?m in aerodynamic diameter, PM(2.5)) pollution in conjunction with high-fat diet induces insulin resistance through alterations in inflammatory pathways. In this study we evaluated the effects of PM(2.5) exposure over a substantive duration of a rodent's lifespan and focused on the impact of long-term exposure on adipose structure and function.Methods and Results: C57BL/6 mice were exposed to PM(2.5) or filtered air (FA) (6 hours/day, 5 days/week) for duration of 10 months in Columbus, OH. At the end of the exposure, PM(2.5)-exposed mice demonstrated insulin resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed group. Although there were no significant differences in circulating cytokines between PM(2.5)- and FA-exposed groups, circulating adiponectin and leptin were significantly decreased in PM(2.5)-exposed group. PM(2.5) exposure also led to ...
Two different reverse osmosis systems were investigated. The first was a 50-element plant-scale system that is used to treat 2200 m"3 of AECL liquid radwastes annually.It uses thin-film composite (TFC) membranes and operates at an applied pressure of 2760 kPa, with a fixed crossflow of about 40 L/min. The other system uses the same thin-film composite membranes for waste processing but is a two-element pilot-scale system. It is operated at pressures m ranging between 1500 and 7000 kPa, at a fixed crossflow of 55 L/min. The average lifetime of the thin-film composite membranes in the plant-scale processing application at AECL is about 3000 h. After this service life has expired the rejection efficiency declines rapidly from 99.5% to about 95% as the membranes become impaired from chemical cleaning procedures that are required after each 100 m"3 of waste is treated. The permeation flux for the plant-scale system decreases from about 2.2 L/min/element to below 0.5 ...
The standard protocol in multislice spiral CT (MSCT) angiography for coronary arteries with fixed tube current-time settings leads to an overexposure and thus to an unnecessary high radiation dose in patients with lower weight when compared to heavier patients. The purpose of this study was to estimate the effect of reducing the radiation dose by adapting the tube current-time settings individually. Fifty patients underwent retrospectively ECG-gated MSCT of the heart. In 25 patients (group A{sub 1}) a standard protocol with constant tube current-time settings was used (4 x 1-mm collimation, 120 kV, 400 mAs{sub eff}). Subsequently, artificial image noise was added to the data of these patients simulating a directive for weight-adapted tube current-time settings (group A{sub 2}). In the other 25 patients (group B) an alternative protocol with individually weight-adapted tube current-time settings was applied. The data of all groups were evaluated by a regression analysis. The image ...
The standard protocol in multislice spiral CT (MSCT) angiography for coronary arteries with fixed tube current-time settings leads to an overexposure and thus to an unnecessary high radiation dose in patients with lower weight when compared to heavier patients. The purpose of this study was to estimate the effect of reducing the radiation dose by adapting the tube current-time settings individually. Fifty patients underwent retrospectively ECG-gated MSCT of the heart. In 25 patients (group A_1) a standard protocol with constant tube current-time settings was used (4 x 1-mm collimation, 120 kV, 400 mAs_e_f_f). Subsequently, artificial image noise was added to the data of these patients simulating a directive for weight-adapted tube current-time settings (group A_2). In the other 25 patients (group B) an alternative protocol with individually weight-adapted tube current-time settings was applied. The data of all groups were evaluated by a regression analysis. The image quality was ...
Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in homozygous null progeny at lower frequencies than expected. Genotyping offspring at pre-, peri-, and postnatal stages revealed that over half of homozygous null mutants die in the early postnatal stages. To investigate the reasons for this early postnatal lethality, we analyzed in detail different parameters in the initial hours after birth. POMC null mutants born to heterozygous dams presented at birth with corticosterone levels no different from wildtype littermates, were euglycemic, and had normal liver glycogen stores. However, already 30 min after birth corticosterone levels dropped by 80% and were undetectable thereafter, while corticosterone levels in wildtype animals increased during postnatal hours. Circulating adrenaline was almost below detection 1h after birth. Blood glucose levels fell sharply in all genotypes within 30 min after birth; however, wildtype and heterozygous pups overcame hypoglycemia ...
Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, ...
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate levels of phospho-S6 and the negative immune regulator B7-H1 in tumor cells, Honokiol does not significantly impair T cell ...
The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of /sup 203/Pb and /sup 47/Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol (1,25(OH)/sub 2/D/sub 3/) as their only source of the vitamin, the absorption of both /sup 47/Ca and /sup 203/Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in /sup 47/Ca and /sup 203/Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)/sub 2/D/sub 3/, the intestinal absorption of /sup ...
The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of "2"0"3Pb and "4"7Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol [1,25(OH)_2D_3] as their only source of the vitamin, the absorption of both "4"7Ca and "2"0"3Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in "4"7Ca and "2"0"3Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)_2D_3, the intestinal absorption of "4"7Ca and of "2"0"3Pb was increased, as well ...
For most cells there exists an optimum cooling rate. Both supraoptimal rates and suboptimal rates can be very damaging. The optimal rate varies enormously from less than or equal to 1/sup 0/C/min for mammalian preimplantation embryos to greater than or equal to 800/sup 0/C/min for the human red cell. Death at supraoptimal rates is the result of the formation of intracellular ice and its recrystallization during warming. Intracellular ice occurs when cells are cooled too rapidly to allow them to equilibrate by the osmotic withdrawal of intracellular water. The definition of too rapid depends chiefly on the size of the cell and its permeability to water. Death at suboptimal rates is a consequence of the major alterations in aqueous solutions produced by ice formation. The chief effects are a major reduction in the fraction of the solution remaining unfrozen at a given temperature and a major increase in the solute concentration of that fraction. Presumably, slow freezing injury is a ...
Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can generate DNA replication checkpoint signals. Efficient removal of those cells in which ...
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid ...
The purpose was to evaluate low-dose CT colonography without cathartic cleansing in terms of image quality, polyp visualization and patient acceptance. Sixty-one patients scheduled for colonoscopy started a low-fiber diet, lactulose and amidotrizoic-acid for fecal tagging 2 days prior to the CT scan (standard dose, 5.8-8.2 mSv). The original raw data of 51 patients were modified and reconstructed at simulated 2.3 and 0.7 mSv levels. Two observers evaluated the standard dose scan regarding image quality and polyps. A third evaluated the presence of polyps at all three mSv levels in a blinded prospective way. All observers were blinded to the reference standard: colonoscopy. At three times patients were given questionnaires relating to their experiences and preference. Image quality was sufficient in all patients, but significantly lower in the cecum, sigmoid and rectum. The two observers correctly identified respectively 10/15 (67%) and 9/15 (60%) polyps {>=}10 mm, with 5 and 8 ...
Polymethlylmethacrylate (PMMA) is the most frequently used cement for percutaneous vertebroplasty and kyphoplasty. To aid visualisation during surgery cements are doped with radiopacifying agents such as Barium sulphate (Ba(2)SO(4)) or Zirconium Dioxide (ZiO(2)). Mounting research suggests that these agents may impair the biocompatibility of the cements. However, incorporating an alternative radiopacifier agent with excellent biocompatibility would be a significant step forward. Bioactive radiopaque glasses incorporating elements such as strontium (Sr) and zinc (Zn), known to have beneficial and therapeutic effects on bone, are of great interest in this respect. In this study, the Ba(2)SO(4) of the commercially available Spineplex was incrementally replaced with a radiopaque therapeutic glass composition. The resulting effects on cement setting time, peak isotherm, ultimate compressive strength, Young's modulus (up to 30 days cement maturation) and radiopacity were ...
Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain ...
Bangladesh possesses many industrial sites, whereby wastes and effluents are directly discharged into the environment without any treatment. Agricultural areas are contaminated thereby and the food quality is impaired. Therefore, the aim of the present work was to develop simple and cost effective strategies to reduce soil-plant transfer of harmful substances. Three sites were selected in the vicinity of Dhaka city (Tongi pharmaceutical, Tejgaon industrial and Hazaribagh tannery area). Field and pot experiments were carried out with different varieties of field crops (rice, wheat and tomato) and different soil amendments (cowdung, city waste compost, oil cake, waterhyacinth, poultry litter, lime and red mud). At the site Tongi, pollutants mainly consists of organic compounds. The soil of Tejgaon is acidic (pH=5.7), contains high organic matter and elevated concentrations of Zn (685 mg/kg), Pb (136 mg/kg), and Cd (2.6 mg/kg). The Hazaribagh region is polluted by a ...
Mutations in transcription factors hepatocyte nuclear factors (HNF)-1#alpha# and HNF-1#beta# cause maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. HNF-1#alpha# and HNF-1#beta# mutations are well studied in some tissues, but the mechanism by which HNF-1#alpha# and HNF-1#beta# mutations affect sucrase-isomaltase (SI) transcription in the small intestine is unclear. We studied the effects of 13 HNF-1#alpha# mutants and 2 HNF-1#beta# mutants on human SI gene transcription, which were identified in subjects with MODY3 and MODY5, respectively. Transactivation activity of 11 HNF-1#alpha# and 2 HNF-1#beta# mutants was significantly lower than that of wild (wt)-HNF-1#alpha# and wt-HNF-1#beta#. Furthermore, in co-expression studies with mutant (mu)-HNF-1#alpha#/ wt-HNF-1#beta# and wt-HNF-1#alpha#/mu-HNF-1#beta#, the combination of mu-HNF-1#alpha# (P379fsdelCT and T539fsdelC)/wt-HNF-1#beta# impaired SI transcription, but the others were not remarkably ...
Increasing prosperity and population-growth in many developing countries are resulting in accelerated growth in population of vehicles and vehicle-kilometers traveled. In Pakistan also, the number of vehicles has jumped from 0.8 million to about 4.0 million within 20 years, showing an overall increase of more than 400%. Accordingly, the consumption of petrol (motor spirit) has increased from 828,670 metric tons to 1,189,042 metric tons. The high content of lead in petrol is a serious issue, as the end- product is the release of lead into the environment. In Pakistan, prior to July 2001, lead-content in petrol was reported to be as high as 0.35-0.84 gram per liter. The reported lead-levels in air (micrograms/cubic centimeter) in different cities of Pakistan are: Karachi (1980-81) 0.13-0.24; Peshawar (1994-95) 0.21-0.79; Lahore (1993-94) 0.15-8.36 and (1999-2000) 0.89-7.85 and Rawalpindi (1999-2000) 0.71-10.00, indicating the very alarming increase and high levels of lead in the ambient ...
Abstract in english Type II reaction in leprosy, or erythema nodosum leprosum (ENL), is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide (more) , can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, ...
The authors present the results of an investigation of the effect of gamma radiation on the properties of low-molecular moulded polymethyl methacrylates (molecular weight distribution, physico-mechanical properties, resistance to the effects of aqueous media and physiological solution) in the form of copolymers of methyl methacrylate with methyl acrylate (MA) or butyl acrylate (BA) with the brand names Dacryl-4B, Dacryl-2M and Dacryl-4M (4% BA; 2 and 4% MA respectively) having a molecular weight of around 10"5. For comparison, block polymethyl methacrylate with a molecular weight of 3 x 10"6 was used. The results of experiments on the ageing of unirradiated and irradiated specimens in a heated store-room (t = 10 - 20"0C) and at high temperatures (90"0C) are also given. It is shown that irradiation with doses of 2.5 - 20 Mrad leads to radiolysis of the above copolymers, accompanied by destructive processes. Evidence of this is an increase in the polydispersity of the materials and a ...
The authors present the results of an investigation of the effect of gamma radiation on the properties of low-molecular moulded polymethyl methacrylates (molecular weight distribution, physicomechanical properties, resistance to the effects of aqueous media and physiological solution) in the form of copolymers of methyl methacrylate with methyl (MA) or butyl acrylate (BA) with the brand names Dacryl-4B, Dacryl-2M and Dacryl-4M (4% BA; 2 and 4% MA respectively) having a molecular weight of around 10"5. For comparison, block polymethyl methacrylate with a molecular weight of 3 x 10"6 was used. The results of experiments on the ageing of unirradiated and irradiated specimens in a heated store-room (t = 10 - 20"0C) and at high temperatures (90"0C) are also given. It is shown that irradiation with doses of 2.5-20 Mrad leads to radiolysis of the above copolymers, accompanied by destructive processes. Evidence of this is an increase in the polydispersity of the materials and a reduction in ...
The health of professional bus drivers is a critical factor in their driving performance; any impairment may lead to undesired consequences. In an attempt to develop and prioritize health and wellness programs, this study investigates the factors significantly affecting the health conditions of professional bus drivers, as well as the strength of these factors. This study uses self-rated health as the examination measurement. This simple assessment is an inclusive measure of health status for judging health trajectory, and is highly associated with changes in functional ability, including perceived control over driving. This study evaluates driver responses of self-rated health with ordered response models that consider factors such as the driver reported health problems, physical and psychological conditions, demographic factors, driving experience, and working environment. Analysis of a sample of 785 drivers shows that age, body mass index, depression, daily ...
Two separate studies address the major issues of deforestation in developing countries, namely, Does deforestation seriously impair the soil-plant system. and How can a steady supply of wood fuels be guaranteed with diminishing natural forest. In Chapter 1, twenty-six cross-sectional and time series studies of soil properties in the US and ten countries between the tropics were examined to determine the changes associated with deforestation in soil organic C, total N, exchangeable Ca, Mg, and K, cation exchange capacity, available P, bulk density, and pH. Deforestation was associated with significant changes in these soil properties. Only bulk density and avaiable P showed any tendency to return to pre-clearing levels. Differences in soil response to deforestation according to climate and age of parent material were related to temperature, rainfall, vegetation, soil acidity, and organic matter production and decomposition on each site. In Chapter 2, a ...
Neuronal transcription factors play vital roles in the specification and development of neurons, including dopaminergic (DA) neurons. Mutations in the gene encoding the purine biosynthetic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause the resulting intractable and largely untreatable neurological impairment of Lesch-Nyhan disease (LND). The disorder is associated with a defect in basal ganglia DA pathways. The mechanisms connecting the purine metabolic defect and the central nervous system (CNS) phenotype are poorly understood but have been presumed to reflect a developmental defect of DA neurons. We have examined the effect of HPRT deficiency on the differentiation of neurons in the well-established human (NT2) embryonic carcinoma neurogenesis model. We have used a retrovirus expressing a small hairpin RNA (shRNA) to knock down HPRT gene expression and have examined the expression of a number of transcription factors essential for neuronal ...
The purpose of the paper is to investigate whether high-resolution CT (HRCT) can detect the subjects with massive emphysematous destruction in a group of patients with severe chronic obstructive pulmonary disease (COPD) and therefor be of help in selecting the candidates to surgical lung volume reduction. Have been examined 40 former smokers with severe COPD (FEV_1#<=#40% of the predicted value, with no major improvement after inhalation of bronchodilators). The emphysema extent score was significantly correlated with the hematocrit value and Tiffeneau index (p<2) in all the 40 patients. The severity of bronchial obstruction was the same in bronchitis and dyspnoeic patients. The subject with chronic bronchitis had milder emphysema (mean extent 35% versus 47% in the dyspnoeic subjects) and a higher frequency of bronchial involvement. A decrease in FEV_1 was significantly correlated with emphysema extent (p<1) in dyspnoeic, but not in bronchitis, patients. Moreover, the former ...
The gender-specific expression pattern of aromatase and 5alpha-reductases (5alpha-R) during brain development provides neurons the right amount of estradiol and DHT to induce a dimorphic organization of the structure. Polychlorinated biphenyls (PCBs) are endocrine disruptive pollutants; exposure to PCBs through placental transfer and breast-feeding may adversely affect the organizational action of sex steroid, resulting in long-term alteration of reproductive neuroendocrinology. The study was aimed at: a) evaluating the hypothalamic expression of aromatase, 5alpha-R1 and 5alpha-R2 in fetuses (GD20), infant (PN12), weaning (PN21) and young adult (PN60) male and female rats exposed to PCBs during development; b) correlating these parameters with the time of testicular descent, puberty onset, estrous cyclicity and copulatory behavior; c) evaluating possible alterations of some non reproductive behaviors (locomotion, learning and memory, depression/anxiety behavior). A reconstituted ...
A typical form of change in runoff characteristics caused by the widespread use of hydroelectric power in Switzerland is the intermittent draining (torrent operation). It is the aim of the present work to help elucidate possible consequences of these changes in drain onto the benthobiocoenosis. The study was carried through on the Secklisbach at Oberrickenbach (in the semicanton of Nidwalden) and one of its side streamlets (800m above sea level). The macroinvertebrate coenosis was studied at four locations with similar conditions of drainage basin, population density and topography but varying in the degree of impairment to the draining. There were monthly benthos samples taken using a Surber sampling-device. Results show that the locations not only varied in drain, but also in temperature, this being a consequence of water storage by the power plant. The readings pointed out different values for the locations in daily average temperature, day amplitudes and ...
Objective: To investigate transcutaneous oximetry as parameter of the microcirculation is correlated to ankle-brachial-index as parameter of the macrocirculation after peripheral angioplasty procedures. Design: Prospective study. Materials and methods: 60 patients suffering from intermittent claudication were scheduled for angioplasty treatment. 45 patients were considered as eligible for angioplasty after angiographic evaluation, 15 patients underwent angiography only. Transcutaneous oximetry measurements were performed before the procedure, at the end of intervention, 24 h as well as 2 and 4 weeks after percutaneous transluminal angioplasty. Ankle-brachial-indices were obtained before intervention, 24 h as well as 2 and 4 weeks later. Results: Ankle-brachial-indices increased significantly at 24 h after angioplasty in patients being treated with angioplasty. Transcutaneous oximetry values dropped significantly at the end of the procedure and returned close to the baseline levels at 2 ...
CT is the most accurate method to detect pulmonary emphysema in vivo. They compared prospectively two different methods for emphysema quantitation in 5 normal volunteers and 20 consecutive patients with chronic obstructive pulmonary disease (COPD). All subjects were submitted to function tests and HRCT; three scans were acquired at preselected levels during inspiration. The type and extent of pulmonary emphysema were defined by two independent observers under blind conditions. Disagreements were subsequently settled by consent. All subjects were also examined with expiratory spiral CT using a density mask program, at two different cut-off levels (-850,-900 HU). Visual score and expiratory spiral density mask values (-850 HU) were significantly correlated (r = 0.86), but the visual extent of emphysema was always higher than shown by expiratory spiral CT. The emphysema extent assessed with both CT methods correlated with the function result of expiratory airflow obstruction and gas ...
Parallel imaging and echo sharing techniques have markedly reduced the acquisition times for MRI of large volumes. Dynamic 2 and 3-dimensional data sets of the chest with high temporal resolution (up to 10 images/s with single slice and 2 volume/s) allow an analysis of respiratory motion of the lungs and tumors. Time-resolved 2D series in preselected planes can be used to observe respiratory motion during free breathing or after respiratory commands, e.g. to exclude chest wall invasion by a tumor or for diagnosing impairment of respiratory mechanics. Time-resolved 3D-series (4D-MRI) allow monitoring of the spatial displacement of the lungs and tumors as a whole volume. Present limitations such as an overestimation of tumor size and an underestimation of displacement due to a limited temporal resolution are expected to be overcome with further technical developments. However, 4D-MRI already appears to be the appropriate tool to select patients for motion-adapted ...
Encapsulation of technetium-99m sestamibi ({sup 99m}Tc-MIBI) in polyethyleneglycol-liposomes ({sup 99m}Tc-MIBI-PEG-liposomes) could extend the duration of its circulation in blood and alter its biodistribution, enabling its concentration in tumours to be increased. An original method to encapsulate {sup 99m}Tc-MIBI in PEG-liposomes is described. The {sup 99m}Tc-MIBI-PEG-liposomes were compared with free {sup 99m}Tc-MIBI with respect to (a) tumour availability (b) ability to distinguish between chemotherapy-sensitive and -resistant cells and (c) uptake ratio in tumour imaging. PEG-liposomal systems composed of distearoylphosphatidylcholine/cholesterol/PEG{sub 2000}-distearoyl phosphatidylethanolamine and lissamine-rhodamine B-labelled liposomes were used. The encapsulation of {sup 99m}Tc-MIBI in liposomes was achieved using the K{sup +} diffusion potential method. We compared the uptake of free versus encapsulated {sup 99m}Tc-MIBI by sensitive and resistant erythroleukaemia (K562) and ...
Shewanella oneidensis MR-1 is a model environmental organism that possesses diverse respiratory capacities, including the ability to reduce soluble Cr(VI) to sparingly soluble, less toxic Cr(III). Effective bioremediation of Cr-contaminated sites requires knowledge of the molecular mechanisms and regulation of heavy metal resistance and biotransformation by dissimilatory metal-reducing bacteria. Towards this goal, our ERSP-funded work is focused on the identification and functional analysis of genes/proteins comprising the response pathways for chromate detoxification and/or reduction. Previous transcriptomic profiling and whole-cell proteomic analyses implicated the involvement of a functionally undefined DNA-binding response regulator (SO2426) and a putative azoreductase (SO3585) in the chromate stress response of MR-1. Here we describe a detailed functional analysis of SO2426 and SO3585 in order to begin to understand the role of these proteins in the cellular response to chromate. ...
High energy piping systems are operated with either or both conditions of maximum operating temperature exceeding 200 .deg. F(93.3 .deg. C) or maximum operating pressure exceeding 275 psig(19.3kg/cm{sup 2}) during normal operating conditions in nuclear power plants. A high energy pipe failure is postulated in branches or piping that runs larger than one inch nominal diameter. The resultant consequences of these postulated pipe breaks must be analyzed for the effect on maintenance of plant safe shutdown capability, containment integrity. And the analyzed results must be applied to the system design so that a pipe failure can not damage essential systems to an extent of impairing design function nor affect necessary component operability. The considerable effects of pipe break are as follows; dynamic effects such as pipe whip, jet impingement and environmental impact by release of system contents. Two types of forces are occurred by the pipe whip. The one is pipe ...
Early recognition of recurrence and work-up of clinically indeterminate lesions may be impaired after reconstruction with silicone implants due to superimposition of the implant or to scarring. This study was undertaken to evaluate the use of contrast-enhanced MRI in patients with silicone implant after breast cancer. Contrast-enhanded MRI was offered to 169 patients. Comparative two- to three-view mammography was also performed in 169 patients, as well as comparative sonography in 144 patients. Conventional imaging and clinical examination detected only 8/13 recurrences, whereas 12/13 were detected by MRI. One recurrence had been visible as a strongly enhancing 2-mm dot in a previous examination (2 years before), but was not called. It was therefore counted as false negative. In addition, multicentricity was detected by MRI alone in two of three cases. MRI correctly diagnosed scar tissue in all cases with indeterminate findings. However, due to false-positive ...
Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder of early childhood onset. Defining symptoms are chronic impairments of attention, impulse control and motor hyperactivity that frequently persist until adulthood. Miscellaneous causes of the disorder have been discussed. Accumulating evidence from imaging- and molecular genetic studies strengthened the theory of ADHS being a predominantly inherited disorder of neurobiological origin. In the last 15 years, non-invasive brain imaging methods were successfully implemented in pediatric research. Functional magnetic resonance imaging studies gave major insight into the neurobiological correlates of executive malfunction, inhibitory deficits and psychomotoric soft signs. These findings are in good accordance with brain morphometric data indicating a significant volumetric decrease of major components of striato-thalamo-cortical feedback loops, primarily influencing prefrontal executive ...