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PubMed1998

Nitric oxide availability in diabetes mellitus.

Diabetes mellitus is associated with early development of cardiovascular complications. Under physiological conditions the endothelium protects against the development of atherosclerosis. Endothelial cells produce, e.g., nitric oxide (NO), a substance which is capable of keeping vascular tone, coagulation and inflammation well balanced. However, in pathological conditions, such as in diabetes mellitus, impaired NO activity may be present. Decreased NO activity can be caused by impaired production of NO, due to uncoupling of receptor-mediated signal transduction, a deficiency of the NO synthase (NOS) substrate L-arginine, or a decreased availability of one or more cofactors essential for optimal functioning of NOS. However, hyperglycaemia also stimulates the production of advanced glycosylated end products, enhances the polyol pathway and activates protein kinase C. These conditions may lead to increased oxidative stress. Reactive oxygen species rapidly inactivate NO leading to the formation of peroxynitrite. Peroxynitrite is a toxic oxidant capable of damaging many biological molecules. Reduced NO availability may not only be of relevance to the development of atherosclerotic complications in diabetes but may also interfere with insulin-mediated postprandial glucose disposal and possibly contribute to the development of insulin resistance. Understanding of the complex metabolic disturbances interacting with the NO system may provide us with further therapeutic options to decrease cardiovascular morbidity and mortality in diabetes mellitus.

Animals↗

PubMed2000

Use of cultured cerebral capillary endothelial cells in modeling the central nervous system availability of 2',3'-dideoxyinosine.

The biochemical and physiological mechanisms responsible for the limited central nervous system (CNS) uptake of dideoxynucleoside reverse transcriptase inhibitors currently used to treat HIV-1 infection in humans are poorly understood. In vitro models of the blood-brain barrier (BBB) offer an attractive alternative to in vivo or in situ animal studies for understanding the role of the blood-brain barrier in regulating brain tissue concentrations of these agents. In the present study, the kinetics of 2', 3'-dideoxyinosine (ddI) uptake and purine nucleoside phosphorylase (PNP) mediated catabolism in primary cultures of bovine brain microvessel endothelial cells (BBMECs) were determined in order to ascertain the importance of both transport and metabolism governing the CNS availability of this purine dideoxynucleoside. Initial rates of ddI uptake as a function of ddI donor concentration suggest the involvement of both passive diffusion and carrier-mediated processes. These studies confirm earlier in vivo findings that transporters may play a role in regulating the CNS concentration of ddI. Analysis of ddI uptake and metabolite accumulation in BBMECs over longer time intervals (beyond the intial rate region) provide substantial in vitro evidence for an enzymatic BBB for ddI. Simulations of the CNS availability of ddI derived from in vitro estimates of parameters for passive diffusion, carrier-mediation, and metabolism indicate that the fraction of ddI entering the BBB cells which actually reaches the brain parenchyma may be quite low (< 2%) due to metabolism by PNP localized within the BBB, consistent with the low CNS delivery of ddI observed in vivo. Transporters and metabolic enzymes within the BBB may function in coordinated fashion to reduce the CNS concentrations of both rapidly metabolized and poorly metabolized dideoxynucleosides.

Animals↗

PubMed2000

Iron availability from processed and cooked wheat products using haemoglobin regeneration efficiency method.

In India, the prevalence of iron deficiency is high due to both low iron intake and low availability from foods of plant origin. We investigated the effect of different wheat products on iron availability by testing haemoglobin regeneration efficiency using a rat model. Wheat grains processed into whole wheat flour, pearled wheat flour and broken wheat were used to prepare chapati, parantha and porridge. All samples were analysed for proximate principles, minerals, namely calcium, iron, zinc, sodium, potassium, fibre, phytin phosphorus and total phenols. Protein, fat, fibre, phytate and total phenols of pearled wheat flour were lower than whole wheat flour. All minerals except zinc were significantly higher (P < 0.001) in whole wheat flour while soluble iron was higher in pearled wheat flour. Cooking resulted in an increase in soluble iron and neutral detergent fibre (P < 0.001) and decrease in phytin phosphorus and total phenols. Haemoglobin regeneration efficiency (HRE) of pearled wheat flour was significantly higher than whole wheat flour. Cooking resulted in significant (P < 0.05) increase in HRE and HRE of chapati was higher than parantha. Soluble iron and HRE were significantly associated.

Anemia↗

PubMed2002

Quantitative comparison and evaluation of two commercially available, two-dimensional electrophoresis image analysis software packages, Z3 and Melanie.

While a variety of software packages are available for analyzing two-dimensional electrophoresis (2-DE) gel images, no comparisons between these packages have been published, making it difficult for end users to determine which package would best meet their needs. The goal here was to develop a set of tests to quantitatively evaluate and then compare two software packages, Melanie 3.0 and Z3, in three of the fundamental steps involved in 2-DE image analysis: (i) spot detection, (ii) gel matching, and (iii) spot quantitation. To test spot detection capability, automatically detected protein spots were compared to manually counted, "real" protein spots. Spot matching efficiency was determined by comparing distorted (both geometrically and nongeometrically) gel images with undistorted original images, and quantitation tests were performed on artificial gels with spots of varying Gaussian volumes. In spot detection tests, Z3 performed better than Melanie 3.0 and required minimal user intervention to detect approximately 89% of the actual protein spots and relatively few extraneous spots. Results from gel matching tests depended on the type of image distortion used. For geometric distortions, Z3 performed better than Melanie 3.0, matching 99% of the spots, even for extreme distortions. For nongeometrical distortions, both Z3 and Melanie 3.0 required user intervention and performed comparably, matching 95% of the spots. In spot quantitation tests, both Z3 and Melanie 3.0 predicted spot volumes relatively well for spot ratios less than 1:6. For higher ratios, Melanie 3.0 did much better. In summary, results suggest Z3 requires less user intervention than Melanie 3.0, thus simplifying differential comparison of 2-DE gel images. Melanie 3.0, however, offers many more optional tools for image editing, spot detection, data reporting and statistical analysis than Z3. All image files used for these tests and updated information on the software are available on the internet (http://www.umbc.edu/proteome), allowing similar testing of other 2-DE image analysis software packages.

Electronic Data Processing↗

PubMed1993

Prevention of epoxy resin dermatitis: failure of manufacturers to use available research information.

Research information is often recommended as a solution for occupational disease and injury. This study asks whether publicly available research information on prevention of a well-documented occupational hazard is acted on by an important sector in industry. The hazard, allergic contact dermatitis (ACD) caused by epoxy resins in paints, is particularly significant for painters, who may have to leave their jobs as a consequence of the condition. No evidence is found, according to a priori criteria, that paint manufacturers/suppliers acted on known prevention measures for epoxy resin ACD that are within their control to implement. The findings suggest that availability of research information alone fails to solve health and safety problems. Recommendations for avenues of direct and indirect enforcement where voluntary implementation is absent in the painting industry are suggested.

Australia↗

PubMed2007

Responses of squirrel monkeys to seasonal changes in food availability in an eastern Amazonian forest.

Tropical forests are characterized by marked temporal and spatial variation in productivity, and many primates face foraging problems associated with seasonal shifts in fruit availability. In this study, I examined seasonal changes in diet and foraging behaviors of two groups of squirrel monkeys (Saimiri sciureus), studied for 12 months in Eastern Brazilian Amazonia, an area characterized by seasonal rainfall. Squirrel monkeys were primarily insectivorous (79% of feeding and foraging time), with fruit consumption highest during the rainy season. Although monkeys fed from 68 plant species, fruit of Attalea maripa palms accounted for 28% of annual fruit-feeding records. Dietary shifts in the dry season were correlated with a decline in ripe A. maripa fruits. Despite pronounced seasonal variation in rainfall and fruit abundance, foraging efficiency, travel time, and distance traveled remained stable between seasons. Instead, squirrel monkeys at this Eastern Amazonian site primarily dealt with the seasonal decline in fruit by showing dietary flexibility. Consumption of insects, flowers, and exudates increased during the dry season. In particular, their foraging behavior at this time strongly resembled that of tamarins (Saguinus sp.) and consisted of heavy use of seed-pod exudates and specialized foraging on large-bodied orthopterans near the forest floor. Comparisons with squirrel monkeys at other locations indicate that, across their geographic range, Saimiri use a variety of behavioral tactics during reduced periods of fruit availability.

Animals↗

PubMed1977

Social organization and food resources availability in primates: a socio-bioenergetic analysis of diet and disease hypotheses.

Data obtained during a field study of two species of nonhuman primates (Alouatta villosa and Ateles geoffroyi) living in the Tikal National Park in Guatemala are used to suggest an answer to the question: To what extent is the existence of a particular form of social organization (group size, structure, and composition) an indication of the amount of energy in the form of food resources available to animals in a particular habitat? Seven researchers working in teams spent 2,318 hours in the field, 1,145 hours of which were in contact with the monkeys. Comparisons of dietary data, estimated energy expenditures, and habitat productivity provide indications of the degree to which a habitat is capable of supporting the energy and other nutritional requirements of howler and spider monkeys living within the study area. These data suggest that much larger populations and different forms of social organizations can be supported by resources available within the habitat.

Alouatta↗

PubMed1995

Ogston gel electrophoretic sieving: how is the fractional volume available to a particle related to its mobility and diffusion coefficient(s)?

The Ogston-Morris-Rodbard-Chrambach model (OMRCM) of gel electrophoresis assumes that the mobility mu of charged particles is proportional to the fractional volume (f) of the gel that is available to them. If the gel is random, as described by Ogston, the (semi-log) Ferguson plot is the method of choice for analyzing experimental data since it permits an estimate of the gel's mean pore size to be made. However, the Ferguson plot is rarely linear; this is usually "explained" by the deformation of the anisotropy of the particle, the nonrandom or variable architecture or the gel, or the onset of some other migration mechanism. Many authors have refined this model, but the original assumption that mu varied; is directly proportional to f has not been seriously examined. Also, the model says nothing of the effect of the field intensity, the connectivity of the gel pores, nor anything about the diffusion coefficient. We have developed a Monte-Carlo computer simulation algorithm to study the electrophoretic sieving of simple particles in gels. In this brief communication, we report important preliminary results which indicate that the basic assumptions of the OMRCM are wrong. We use a two-dimensional periodic gel since the OMRCM becomes trivial in this case. Our results show that the relationship between f and mu is not the one assumed by the OMRCM. Moreover, we find that the Einstein relation between the diffusion coefficient and the mobility is not valid. This is due to the fact that the particles do not have a uniform probability of visiting the various sites that are available to them. We thus conclude that the Ferguson plot is intrinsically nonlinear; the curvature of the plot is, in fact, related to the intensity of the electric field as well as to the degree of randomness of the gel fibers.

Algorithms↗

PubMed1995

A Saccharomyces cerevisiae Internet protein resource now available.

The QUEST Protein Database Center is now making available two Saccharomyces cerevisiae protein databases via the Internet. The yeast electrophoretic protein database (YEPD) is a database of approximately one hundred protein identifications on two-dimensional gels. The yeast protein database (YPD) is a database of gene names and properties of over 3500 yeast proteins of known sequence. These databases can be accessed via a World-Wide Web (WWW) server (URL http:@siva.cshl.org). YPD is available via public ftp (isis.cshl.org) as well, in a spreadsheet format, and in ASCII format. When accessed via WWW, both of these databases have hypertext links to other biological data, such as the SWISS-PROT protein sequence database and the Saccharomyces Genome Database (SacchDB), and to each other.

Computer Communication Networks↗

PubMedDate not supplied

Removal of tumour cells from bone marrow: an evaluation of the available techniques.

Autologous bone marrow transplantation has offered a way of increasing the dose of drugs and radiotherapy which can be used to treat patients with malignant disease in an attempt to eradicate tumour. Bone marrow is taken prior to treatment and returned to the patient to 'rescue' haemopoietic function after ablative therapy is completed. Bone marrow removed for autograft may be contaminated with tumour cells at the time of harvest, and it is undesirable to return these to patients even though there are little data available concerning the number of tumour cells necessary to reseed various malignancies. This review considers the various methods available for removing tumour cells from bone marrow destined for autologous transplantation, and evaluates their advantages and disadvantages.

Animals↗

PubMed1985

The distribution and impact of health resource availability in China.

Since 1949, China's progress in mortality reduction has far exceeded that experienced by other developing countries with comparable levels of national income. This achievement has taken place in the context of a development strategy oriented, in part, to the elimination of the worst aspects of poverty. Using recent cross-section data, this paper provides a statistical assessment of the extent to which health resources are evenly distributed in contemporary China, and the degree to which improvements in health resource availability may account for the observed variation in mortality levels. Contrary to expectation, the analysis finds that substantial inequalities do remain in the distribution of health resources, and that these differentials are principally associated with levels of urban income and urbanization. However, these differences in health resource availability do not appear to explain the significant variation which also persists in mortality levels, a finding consistent with the results of similar analyses for developed countries.

China↗

PubMed1994

Altered transcriptional response to nutrient availability in hypovirus-infected chestnut blight fungus.

The gene lac-1, encoding the enzyme laccase, is one of several genes of the chestnut blight fungus, Cryphonectria parasitica, that are suppressed by virulence-attenuating mycoviruses of the hypovirus group. Two antagonistic regulatory pathways have been shown to govern the activity of the lac-1 promoter: a positive pathway that stimulates transcription and a negative pathway that represses transcription. We now report that these two regulatory pathways respond independently to specific changes in the nutritional environment. These newly defined conditions were used to confirm that a hypovirus suppresses the activity of the positive regulatory pathway, and to implicate calmodulin and calcineurin as components of the signal transduction cascades regulating lac-1 transcription. Significantly, lac-1 transcript accumulation was shown to be affected by amino acid availability. Further analysis revealed that transcriptional repression mediated by the negative regulatory pathway is relieved under conditions of amino acid deprivation. Thus, by blocking the positive pathway, hypovirus infection prevents increased lac-1 transcript accumulation in response to amino acid deficiency. These observations are consistent with the hypothesis that hypoviruses alter the transcriptional response of the host fungus to changes in nutrient availability.

Ascomycota↗

PubMed1995

Coordinate expression of coproporphyrinogen oxidase and cytochrome c6 in the green alga Chlamydomonas reinhardtii in response to changes in copper availability.

To maintain photosynthetic competence under copper-deficient conditions, the green alga Chlamydomonas reinhardtii substitutes a heme protein (cytochrome c6) for an otherwise essential copper protein, viz. plastocyanin. Here, we report that the gene encoding coproporphyrinogen oxidase, an enzyme in the heme biosynthetic pathway, is coordinately expressed with cytochrome c6 in response to changes in copper availability. We have purified coproporphyrinogen oxidase from copper-deficient C.reinhardtii cells, and have cloned a cDNA fragment which encodes it. Northern hybridization analysis confirmed that the protein is nuclear-encoded and that, like cytochrome c6, its expression is regulated by copper at the level of mRNA accumulation. The copper-responsive expression of coproporphyrinogen oxidase parallels cytochrome c6 expression exactly. Specifically, the copper-sensing range and metal selectivity of the regulatory components, as well as the time course of the responses, are identical. Hence, we propose that the expression of these two proteins is controlled by the same metalloregulatory mechanism. Our findings represent a novel metalloregulatory response in which the synthesis of one redox cofactor (heme) is controlled by the availability of another (Cu).

Amino Acid Sequence↗

PubMedDate not supplied

Review of oximes available for treatment of nerve agent poisoning.

A review was conducted of papers describing the use of N-methyl-2-pyridinealdoxime (PAM), toxogonin or HI-6 as antidotes to the nerve agents tabun, sarin, soman and VX. The review included use of the oxime alone, oxime plus atropine and oxime plus atropine plus diazepam, given therapeutically, i.e. after nerve agent, in all cases. Experiments with any of these compounds given prophylactically were not considered. The review also included protocols of pyridostigmine prophylaxis and oxime-atropine therapy (with or without diazepam). It was difficult to draw conclusions as to the best oxime to use, because of lack of data in many cases. The identity of the oxime did not appear to be important when pyridostigmine prophylaxis was combined with atropine-oxime-diazepam therapy; in these cases, very good protection was observed in guinea pigs against all four nerve agents. The choice of oxime based on the data presently available may well depend on factors other than protection against lethality, such as cost and availability of the oxime and human toxicity of the oxime. This last factor was also reviewed, and the results showed that toxogonin is likely to cause more side-effects than PAM or HI-6. The efficacy of the oximes against the emerging threat agent GF was also reviewed.

Animals↗

PubMed1994

Current status of available standards for quality improvement of assays for detection of autoantibodies to nuclear and intracellular antigens.

Considerable progress has been made in the improvement of clinical assays for the detection of autoantibodies to nuclear and intracellular antigens with the use of available World Health Organization (WHO) and Arthritis Foundation/Centers for Disease Control (AF/CDC) standards. The ultimate goal of standardization is for various clinical laboratory test results to be interchangeable and for an exchange of data to be done with confidence. This report discusses the available standards. In addition, significant technical problems and variations in methodologies for the detection of autoantibodies to intracellular antigens noted during a 4-year study by a European Consensus Study Group are detailed. Currently, there is a need for a future generation of reference preparations and standards that will show specific antibody reactivity on sensitive enzymes and immunoblotting assays. Standardization efforts should be done to characterize specific nuclear and cellular antigen preparations that may be of natural or of recombinant technology origin.

Antibodies, Antinuclear↗

PubMed2005

A database of recombinant viruses and recombinant viral vectors available from the RIKEN DNA bank.

BACKGROUND: Viral vectors are required as gene-delivery systems for gene therapy and basic research. Recombinant adenoviruses (rAds) expressing genes of interest are being developed as research tools and many studies in vitro and in vivo have already been performed with such rAds. METHODS: Shuttle vectors for rAds were constructed with full-length cDNAs and rAds were generated in HEK293 cells by the COS-TPC method. The rAds and shuttle vectors were developed by the Japanese research community and deposited in the RIKEN DNA Bank (RDB; http://www.brc.riken.jp/lab/dna/en/) for distribution to the scientific community. The Recombinant Virus Database (RVD; http://www.brc.riken.jp/lab/dna/rvd/) was established at the RIKEN BioResource Center (BRC) in Japan as the source of information about and distribution of the various resources. RESULTS: The RIKEN BRC is releasing more than 300 recombinant viruses (RVs) and 500 shuttle vectors, as well as all related information, which is included in a newly established database, the RVD. The RVD consists of (i) information about the RVs, the inserted cDNAs and the shuttle vectors; (ii) data about sequence-tagged sites (STSs) that are markers of viral DNAs; and (iii) experimental protocols for the use of RVs. CONCLUSIONS: The new database and available resources should be very useful to scientists who are studying human gene therapy and performing related basic research. It is a web-interfaced flat-file database that can be accessed through the internet. Moreover, all of the resources deposited in the RDB, which is a public facility in Japan, are available to researchers around the world.

Adenoviridae↗

PubMed2004

Effect of manipulation of iron storage, transport, or availability on myelin composition and brain iron content in three different animal models.

Several observations suggest that iron is an essential factor in myelination and oligodendrocyte biology. However, the specific role of iron in these processes remains to be elucidated. This role could be as an essential cofactor in metabolic processes or as a transcriptional or translational regulator. In this study, we used animals models each with a unique defect in iron availability, storage, or transfer to test the hypothesis that disruptions in these mechanisms affect myelinogenesis and myelin composition. Disruption of iron availability either by limiting dietary iron or by altering iron storage capacity resulted in a decrease in myelin proteins and lipids but not the iron content of myelin. Among the integral myelin proteins, proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results not only in hypomyelination but also in a decrease in myelin compaction. Mice deficient in transferrin must receive transferrin injections beginning at birth to remain viable, and these mice had increases in all of the myelin components and in the iron content of the myelin. This finding indicates that the loss of endogenous iron mobility in oligodendrocytes could be overcome by application of exogenous transferrin. Overall, the results of this study demonstrate how myelin composition can be affected by loss of iron homeostasis and reveal specific chronic changes in myelin composition that may affect behavior and attempts to rescue myelin deficits.

Animals↗

PubMed1986

Noninvasive measurement of spinal cord conduction: review of presently available methods.

The ability to measure spinal cord conduction velocity noninvasively is limited by available methodology. Surface recording of small spinal potentials, although feasible in infants and young children, is problematical in adults, especially when recording over the cervical spine. On the other hand, indirect methods designed to improve the signal-to-noise ratio, which include recording of somatosensory cortical evoked potentials, F-waves, or other muscle responses, are limited by the unproven assumptions necessary in calculating spinal conduction. Additionally, each method has its own particular limitations. The majority of presently available noninvasive methods take a restricted, or no, account of conduction through the motor pathways. Despite these often serious limitations, each of the reviewed methods does play a useful clinical role in the electrophysiologic investigation of cord disease that is not visible radiologically. Knowledge of them allows for sufficient diversity to tackle most relevant problems until an ideal physiologic method is developed.

Biophysical Phenomena↗