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PubMedDate not supplied

[Renal effects of low doses of mercury].

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.

Adult↗

PubMed1998

Effect of hexachlorocyclohexane on hsp26 expression in transgenic Drosophila melanogaster.

Hexachlorocyclohexane (HCH) at different concentrations (0.5 to 5.0 ng/ml) mixed with food was fed to third instar larvae of hsp26-lacZ transgenic Drosophila for 2 hr and hsp26 gene expression was examined by beta-galactosidase staining. Puffing in salivary gland polytene chromosomes was also studied. Brain and midgut of larvae showed dark blue staining at 2.0 and 5.0 ng/ml of HCH. Absence of induced puffing at 67B and 84D in the salivary gland polytene chromosomes indicated that these glands are not affected. The study suggests presence of the vulnerable sites in larvae to the higher concentrations of HCH.

Animals↗

PubMed2006

Hormone fatty acid modifications: gram negative bacteria and vertebrates demonstrate common structure and function.

Bacteria are known to regulate diverse physiological processes through a mechanism called quorum sensing (QS). Prokaryotes communicate by extracellular signalling compounds, i.e. autoinducers (acyl homoserine lactone, AHL of Gram negative bacteria) or pheromones (post-translationally modified peptides of Gram positive bacteria), which activate genetic pathways when they reach a sufficient concentration (QS). A large number of Gram-negative quorum-sensing systems studied so far utilize N-acyl homoserine lactones as signal molecules. In vertebrates small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. GH release is stimulated by hypothalamic GH-releasing hormone (GHRH) and ghrelin (endogenous ligand of the GHS-receptor, GHS-R). Ghrelin is a 28-amino acid peptide, in which the serine-3 (Ser3) is n-octanoylated, and this modification is essential for ghrelin's activity. Ghrelin is the first known case of a peptide hormone modified by a fatty acid. The major active form of ghrelin is a 28-amino acid peptide with octanoylated Ser3; one of the more represented bacterial autoinducers is the N-Octanoyl-DL-homoserine lactone (C8-HL) molecule. The authors hypothesize that Gram-negative bacteria and vertebrates have a functional similarity in the search of food and an important structural homology of AHL and ghrelin for the highly conserved Serine-acylated motive in both molecules. Our suggestions could help one to understand the convergent origin and the biologic meaning of the Serine-acylated group in these organisms, a biologic meaning very important due to the high conservation in two kingdoms which are so different.

Amino Acid Sequence↗

PubMed1996

Ex vivo manipulation of cell subsets for cell therapies.

Large-scale cell separation and ex vivo expansion technologies will form the basis for development of new cellular products for the treatment of cancer and fatal viral diseases. The cell subsets that are likely to play a significant role in cellular therapy include hematopoietic stem cells, platelet and granulocyte precursors, cytotoxic lymphocytes, and genetically modified hematopoietic or lymphoid precursors. Cell enrichment techniques are required to eliminate tumor cells from autologous stem cell grafts and to reduce the size of culture systems required for expansion or gene transfection. The consumption of expensive culture components such as cytokines and serum may be reduced by the use of perfusion bioreactor devices. Methods that have been developed for the production of cell subsets for cellular therapy are reviewed.

Blood Platelets↗

PubMed2002

Rapid and sensitive oligonucleotide ligation assay for detection of mutations in human immunodeficiency virus type 1 associated with high-level resistance to protease inhibitors.

A sensitive, specific, and high-throughput oligonucleotide ligation assay (OLA) for the detection of genotypic human immunodeficiency virus type 1 (HIV-1) resistance to Food and Drug Administration-approved protease inhibitors was developed and evaluated. This ligation-based assay uses differentially modified oligonucleotides specific for wild-type or mutant sequences, allowing sensitive and simple detection of both genotypes in a single well of a microtiter plate. Oligonucleotides were designed to detect primary mutations associated with high-level resistance to amprenavir, nelfinavir, indinavir, ritonavir, saquinavir, and lopinavir, including amino acid substitutions D30N, I50V, V82A/S/T, I84V, N88D, and L90M. Plasma HIV-1 RNA from 54 infected patients was amplified by reverse transcription-PCR and sequenced by using dideoxynucleotide chain terminators for evaluation of mutations associated with drug resistance. These same amplicons were genotyped by the OLA at positions 30, 50, 82, 88, 84, and 90 for a total of 312 codons. The sensitivity of detection of drug-resistant genotypes was 96.7% (87 of 90 mutant codons) in the OLA compared to 92.2% (83 of 90) in consensus sequencing, presumably due to the increased sensitivity of the OLA. The OLA detected genetic subpopulations more often than sequencing, detecting 30 mixtures of mutant and wild-type sequences and two mixtures of drug-resistant sequences compared to 15 detected by DNA sequencing. Reproducible and semiquantitative detection of the mutant and the wild-type genomes by the OLA was observed by analysis of wild-type and mutant plasmid mixtures containing as little as 5% of either genotype in a background of the opposite genome. This rapid, simple, economical, and highly sensitive assay provides a practical alternative to dideoxy sequencing for genotypic evaluation of HIV-1 resistance to antiretrovirals.

Base Sequence↗

PubMed2005

Regulatory issues for plant-made pharmaceuticals and vaccines.

Recombinant plant systems potentially offer economic alternatives to produce large amounts of pharmaceutical proteins, including those used in subunit vaccines. Plant systems also provide a convenient oral delivery option, overcoming the cost and inconvenience of purification and injections. The production of pharmaceutical proteins in transgenic plants is tightly regulated, with the US Department of Agriculture focusing on containment of recombinant material and the US Food and Drug Administration focusing on the production system as it relates to manufacture of the drug or vaccine. Current regulations for the production of plant-made pharmaceuticals are to prevent recombinant proteins from entering the food chain or from persisting in the environment, and to guard against recombinant nucleic acid sequences entering genomes of food or feed crops, or wild species. Several alternative plant production systems are being developed. Each system has its strengths and weaknesses with regard to the economics of production, options for alternative routes of administration, authenticity of products and ease with which the production system can be contained. Risk assessments can be used as a means to quantify risks of inadvertent human or environmental exposure to plant-made pharmaceuticals. Several technologies are being tested that reduce the probability of plant-made pharmaceuticals, or genes encoding them, escaping production sites.

Animals↗

PubMed2003

Dietary intake and bone status with aging.

Osteoporosis and related fractures represent major public health problems that are expected to increase dramatically in importance as the population ages. Dietary risk factors are particularly important, as they are modifiable. However, most of the attention to dietary risk factors for osteoporosis has focused almost exclusively on calcium and vitamin D. Recently, there has been considerable interest in the effects of a variety of other nutrients on bone status. These include minerals--magnesium, potassium, copper, zinc, silicon, sodium; vitamins--vitamin C, vitamin K, vitamin B12, vitamin A; and macronutrients--protein, fatty acids, sugars. In addition, foods and food components, including milk, fruit and vegetables, soy products, carbonated beverages, mineral water, dietary fiber, alcohol and caffeine have recently been examined. Together the evidence clearly suggests that prevention of bone loss through diet is complex and involves many nutrients and other food constituents. For many, results remain inconclusive and in some cases contradictory. However, it is increasingly clear that our exposure to a complex of nutrients and food constituents interacts to affect bone status. In addition to identifying the role of individual components, there is a great need to understand the interactions of these factors within diets and, increasingly, in the presence of nutrient supplements. Furthermore, genetic factors are likely to interact with these dietary exposures, increasing the complexity of these effects. With advances in both genetics and nutrition, improved understanding of all these interactions will contribute to effective recommendations for prevention of bone loss and osteoporosis in the aging population.

Aging↗

PubMed1993

Feed and animal factors influencing milk fat composition.

Genetic selection for increased milk fat percentage leads to increased proportions of short-chain fatty acids in milk fat and decreased proportions of long-chain fatty acids. Milk fat composition is strongly influenced by stage of lactation; proportion of short chains (de novo synthesis) is low initially and increases until at least 8 to 10 wk into lactation. Milk fat composition is changed more by the amount and composition of dietary fat than any other dietary component. Seasonal and regional differences in milk fat composition are measurable, most likely because of local differences in feed supplies. Milk fat composition can be modified readily by changing the feeding regimen. The most significant changes in milk fat quality relate to rheological (melting) properties, which influence numerous aspects of character and quality of manufactured dairy products. Dietary fat fed to change milk fat composition may also influence contents of protein, urea, citrate, and soluble calcium in milk and influence oxidative stability and flavor. It is important for both dairy nutritionists and dairy food chemists to understand the consequences of feeding programs on milk quality.

Animal Feed↗

PubMedDate not supplied

Sweet liking and family history of alcoholism in hospitalized alcoholic and non-alcoholic patients.

The present study was designed to test the hypothesis that preference for stronger sweet solutions may be associated with the genetic risk for alcoholism. Thirty-two male patients with alcohol dependence admitted for alcoholism in-patient treatment and 25 non-alcoholic control subjects were used in the study. Hedonic response to sweets was evaluated using the sweet preference test. Family history of alcoholism was evaluated using a Russian version of the Michigan Alcoholism Screening Test modified for the assessment of the alcohol-related behaviour of the subject's biological father. Similar to our previous findings, alcoholics were far more likely to prefer the highest offered sucrose concentration (0.83 M), compared to non-alcoholic controls. Such preference was determined by two factors: positive family history of alcoholism and alcoholic status. Statistically, these factors contributed to the likelihood of preferring sweet solutions independently. Therefore, the effects of these factors may enhance each other. These findings support the hypothesis that preference for a stronger sweet solution is associated with a paternal history of alcohol dependence and may reflect a genetic predisposition to alcoholism.

Adult↗

PubMed2002

Perspectives on the chemical etiology of breast cancer.

Multiple factors, known and unknown, contribute to human breast cancer. Hereditary, hormonal, and reproductive factors are associated with risk of breast cancer. Environmental agents, including chemical carcinogens, are modifiable risk factors to which over 70% of breast cancers have been attributed. Polymorphisms of drug-metabolizing enzymes may influence risk of breast cancer from environmental chemicals, dietary agents, and endogenous steroids. The environmental factors discussed in this review include pollutants, occupational exposures, tobacco smoke, alcohol, and diet. Aromatic amines are discussed as potential mammary carcinogens, with a focus on heterocyclic amine food pyrolysis products. These compounds are excreted into the urine after consumption of meals containing cooked meats and have recently been detected in the breast milk of lactating women.

Adult↗

PubMed2003

Sustainability of insect resistance management strategies for transgenic Bt corn.

Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met thorough the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such analysis is the deployment of transgenic crops. The new transgenic pesticidal or plant-incorporated protectant (PIP) crops have seen widespread application in the United States based on the features of higher yield, lower applications of insecticides, and control of mycotoxin content. However, open rejection of these new crops in Europe and in other countries has been a surprising message and has limited their worldwide acceptance. The US Environmental Protection Agency's (USEPA) Office of Pesticide Programs (OPP) has worked on the development and analysis of insect resistance management (IRM) strategies and has mandated specific IRM requirements for Bacillus thuringiensis (Bt) crops since 1995 under the Food, Fungicide, Insecticide, and Rodenticide Act. Improvement of data quality and sustainability of IRM strategies have been targeted in an ongoing partnership between the USEPA Office of Research and Development and the Office of Pesticide Programs that will further enhance the agency's ability to develop sustainable insect resistance management strategies for transgenic field corn (Bt corn) producing B. thuringiensis (Bt) insecticidal proteins.

Animals↗

PubMedDate not supplied

Biotech pharmaceuticals and biotherapy: an overview.

Broadly, the history of pharmaceutical biotechnology includes Alexander Fleming"s discovery of penicillin in a common mold, in 1928, and the subsequent development-prompted by World War II injuries-of large-scale manufacturing methods to grow the organism in tanks of broth. Pharmaceutical biotechnology has since changed enormously. Two breakthroughs of the late 1970s became the basis of the modern biotech industry: the interspecies transplantation of genetic material, and the fusion of tumor cells and certain leukocytes. The cells resulting from such fusion-hybridomas-replicate endlessly and can be geared to produce specific antibodies in bulk. Modern pharmaceutical biotechnology encompasses gene cloning and recombinant DNA technology. Gene cloning comprises isolating a DNA-molecule segment that corresponds to a single gene and synthesizing ("copying") the segment. Recombinant DNA technology, or gene splicing, comprises altering genetic material outside an organism-for example, by inserting into a DNA molecule a segment from a very different DNA molecule-and making the altered material (recombinant DNA) function in living things. Recombinant DNA technology enables modifying microorganisms, animals, and plants so that they yield medically useful substances, particularly scarce human proteins (by giving animals human genes, for example). This review, however, focuses not on pharmaceutical biotechnology"s methods but on its products, notably recombinant pharmaceuticals. It describes various types of biotech pharmaceuticals, their safety and effectiveness relative to the safety and effectiveness of conventionally produced pharmaceuticals, and the regulation of biotech pharmaceuticals.

Animals↗

PubMed2004

[Advances in the research of genetic engineering of heavy metal resistance and accumulation in plants].

Using plants to remove or inactivate heavy metal pollutants from soils and surface waters provide a cheap and sustainable approach of Phytoremediation. However, field trials suggested that the efficiency of contaminant removal using natural hyperaccumulators is insufficient, due to that many of these species are slow growing and produce little shoot biomass. These factors severely constrain their potential for large-scale decontamination of polluted soils. Moreover, both the micronutrient and toxic metal content accumulated in crops determine the quality and safety of our food-chain. By a transgenic approach, the introduction of novel genes responsible for hyperaccumulating phenotype into high biomass plants and/or stable crops uptaking minerals as food is a promising strategy for the development of effective techniques of phytoremediation and improvement of nutritional value of stable food through a viable commercialization. Recently, the progress at molecular level for heavy metal uptaking, detoxification and hyperaccumulation in plants, and also the clarification of some functional genes in bacteria, yeasts, plants and animals, have advanced the research on genetic engineering plants of heavy metal resistance and accumulation, and on the functional genes (e . g. gsh1, MerA and ArsC) and their genetic transformated plants. These studies demonstrated commercialization potentials of phytoremediation. In this paper, the molecular approach, effects and problems in gene transformation were discussed in details, and also the strategy and emphases were probed into the future research.

Biodegradation, Environmental↗

PubMed2005

Expression of porcine prorelaxin in transgenic tobacco.

In vitro studies demonstrate that porcine relaxin may possess various therapeutic effects. In this study, we explore the possibility of expressing porcine relaxin in transgenic tobacco. Tobacco was selected because it is a non-food, non-feed crop, and recombinant protein production can readily be scaled up. The cDNA of porcine preprorelaxin was under the regulation of two different constitutive promoters. DNA analysis by polymerase chain reaction verified that all transgenic plants contained the correct size of gene insert. Preliminary studies showed the presence of putative prorelaxin bands in both silver-stained SDS-PAGE and western blot. The results also indicated that tobacco-produced prorelaxin may not be properly processed to yield the mature relaxin.

Animals↗

PubMed2003

Expression of a Streptomyces 3-hydroxysteroid oxidase gene in oilseeds for converting phytosterols to phytostanols.

Plant sterols and their hydrogenated forms, stanols, have attracted much attention because of their benefits to human health in reducing serum and LDL cholesterol levels, with vegetable oil processing being their major source in several food products currently sold. The predominant forms of plant sterol end products are sitosterol, stigmasterol, campesterol and brassicasterol (in brassica). In this study, 3-hydroxysteroid oxidase from Streptomyces hygroscopicus was utilized to engineer oilseeds from rapeseed (Brassica napus) and soybean (Glycine max), respectively, to modify the relative amounts of specific sterols to stanols. Each of the major phytosterols had its C-5 double bond selectively reduced to the corresponding phytostanol without affecting other functionalities, such as the C-22 double bond of stigmasterol in soybean seed and of brassicasterol in rapeseed. Additionally, several novel phytostanols were obtained that are not produced by chemical hydrogenation of phytosterols normally present in plants.

3-Hydroxysteroid Dehydrogenases↗

PubMed2003

Naturalness and the genetic modification of animals.

In the past few years it has been recognised that so-called intrinsic concerns about genetic modification (GM) of plants and animals, for food in particular, have an important role in the public perception of GM. One of these concerns is the view that GM is 'unnatural'. This article gives an overview of the often conflicting views on the argument of unnaturalness in books and reports. The author gives a new direction to this discussion, by contrasting the common sense view of nature and animals, with the scientific concept of nature and what is natural. The view of nature and what is natural is always normative. This is illustrated by making explicit the concept of nature in organic farming, which explains why GM is rejected.

Animals↗

PubMed2006

[Association of polymorphism of low density lipoprotein receptor-related protein 5 Q89R, A1330V with bone mineral density in premenopausal northern Chinese women].

OBJECTIVE: To investigate the association of lipoprotein receptor-related protein 5 (LRP5) gene Q89R, A1330V polymorphism with bone mineral density (BMD) in premenopausal Northern Chinese women. METHODS: 283 unrelated healthy residents of Han nationality in Harbin, aged 20 - 50, were selected. All subjects completed a food frequency questionnaire administered by a trained dietitian to estimate dietary calcium intakes, and were measured values of biochemical and hormone, such as the level of serum calcium, serum phosphorus, alkaline phosphatase, parathyroid hormone, calcitonin, 25 (OH) D3, 1, 25 (OH)2D3. The BMD phenotypes were measured by dual energy X-ray densitometry. The polymorphisms of LRP5 gene were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of LRP5 genotype QQ, QR, AA and AV were 83.4%, 16.6%, 64.3% and 35.7% in all subjects. It failed to find that the values of serum biochemistry and the levels of hormones were statistically different among genotypes. Stepwise multiple regression analysis showed that the strongest predictor for BMD was body weight, other significant predictors were age and LRP5 genotypes, A1330V polymorphism were associated with BMD at lumbar spine, however Q89R polymorphism were associated with BMD at shaft and total hip (P = 0.033 and 0.034 respectively). CONCLUSION: LRP gene polymorphism was predictor for BMD in Northern Chinese premenopausal women, BMD at various were modified by different genetic and lifestyle factors in female.

Adult↗

PubMed1994

Atopic dermatitis: recent trends in pathogenesis and therapy.

Emerging concepts in the areas related to the pathogenesis and treatment of atopic dermatitis are reviewed. In particular, recent findings have revealed several key steps in the maintenance of a vicious circle of spongiotic dermatitis associated with elevated T-lymphocyte activation, hyperstimulatory Langerhans cells, defective cell-mediated immunity, and B-cell IgE overproduction. The discovery of specific IgE-binding structures on Langerhans cells provides a mechanism for Langerhans cells to capture and present IgE-targeted allergens to allergen-specific T cells. Furthermore, certain microbial allergens that tend to preferentially elicit IgE-type responses also elicit a T-cell response dominated by the IgE-inducing lymphokine interleukin 4. Repeated stimulation by activated Langerhans cells appears to induce just such a response. Abnormal biochemical responsiveness and mediator release by AD monocytes, mast cells, and eosinophils also participate in the sustainment or initiation of such a vicious circle, and contribute directly to the dermatitis as well. Developments in the areas of neuropeptides, genetics, microbial superantigens, and cytokine networks in the skin also appear to have promise in providing a rational link between immune defects and the inflammatory events in AD. Conventional therapy remains the mainstay of atopic dermatitis management; however, new therapies based upon the above concepts are being tested in clinical trials. Although the difficulty of objectively grading AD lesional activity and the high placebo response of AD patients hampers the interpretation of many reports, several types of approaches are coming into focus. The effectiveness of cyclosporin A, which targets T-cell activation and antigen presentation, indicates that additional agents with such activity should be effective, and verifies the criticality of these cells in AD pathogenesis. Therapy with biologic response modifiers, such as interferon gamma or thymopentin, is oriented toward normalization of imbalanced immune responsiveness, rather than direct suppression of the immune system. The mechanism of action of and toxicities of Chinese herbal mixtures require further investigation, but may reveal hitherto unconsidered avenues. Other recent therapeutic trials have focused on reduction of trigger factors, such as house dust mite exposure, foods, and the abnormal epidermal lipid barrier to irritation.

Dermatitis, Atopic↗