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At least 631 records · Page 35Linked to original sources

PubMed1983

DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo.

Glucocorticoids stimulate transcriptional initiation within integrated mammary tumor virus (MTV) DNA sequences in infected cells. We report here that production of herpes simplex virus thymidine kinase (tk) RNA is stimulated as much as 50-fold by the glucocorticoid, dexamethasone, when sequences from a particular region of MTV DNA are fused upstream of the normally constitutive tk promoter region. Three cloned fragments of MTV DNA were tested, each itself lacking the sequences required for transcription initiation. We monitored the effects of dexamethasone on the efficiency with which these recombinants transfect a tk- rat cell line to a tk+ phenotype, and measured tk enzymatic activity, the size and abundance of tk mRNA, and the 5' termini of tk transcripts in the transfectants. We conclude that the MTV promoter region contains a "glucocorticoid response element" that can be separated from a second element essential for MTV transcription initiation. The hormone response element maps within a 340-base pair MTV DNA fragment that contains specific binding sites for purified glucocorticoid receptor protein in vitro, implying that receptor binding at these sites in vivo may mediate hormone responsiveness. Comparison of several different constructions indicates that the location and orientation of the glucocorticoid response element relative to the transcription start site is not rigidly constrained.

Animals↗

PubMed2000

Modulation of gastrointestinal inflammation by chimeric proteins in experimental models.

Conventional drug therapy in patients with chronic gastrointestinal inflammation is clinically effective in the majority of patients. However, in a relevant group of patients with highly active disease refractory to conventional drugs and for patients with severe side effects new therapeutic strategies are necessary. An advanced understanding of the immune mechanisms underlying chronic diseases resulted in the possibility to use chimeric proteins, in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines for specific immunomodulation. The immunomodulating effects of chimeric proteins such as CTLA-4-IgG, interleukin-10-IgG, IL-2-IgG or tumour necrosis factor (TNF)-receptor IgG have been proven beneficial in a variety of in vitro and in vivo models of chronic gastrointestinal inflammation and autoimmune diseases. It thus seems likely that genetically engineered fusion proteins targeting specific elements of the immune response may become an essential element in new clinical treatment protocols.

Animals↗

PubMedDate not supplied

Set, setting, and matrix.

The future use of psychedelics as an aid to therapeutic change is bound to come. The best source of information on how to use these extraordinary drugs is clearly a detailed description of the successes (and failures) of those researchers who have used these compounds to bring curative, creative and growth-potentiating experiences to their patients. A study of their work is recommended in order to identify those elements that lead to successful sessions. Two known essential elements are "set," which involves the personality and experiences of the patient, and "setting," which has to do with the environment of the session. A third element of importance is that of "matrix," which includes consideration of the environment (1) from which an individual comes, (2) in which the individual lives during the time of the sessions, and (3) to which the individual returns after successful therapy--the everyday living space; these three elements are discussed.

Hallucinogens↗

PubMed1996

Immunomodulation in experimental and clinical nephrology using chimeric proteins.

The objective of immunosuppressive therapy in nephrology is to prevent autoimmune diseases and to suppress kidney allograft rejections while sparing other effects. Increased clarification of the underlying immune mechanism has made specific immunodulation possible using chimeric proteins in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines. The immunosuppressive effects of fusion proteins such as CTLA-4 IgG, CD40 IgG, interleukin (IL)-10 IgG, IL-2 IgG or tumor necrosis factor (TNF)-receptor IgG have been proven in various animal models. Moreover, the application of TNF-receptor IgG successfully limited the OKT3-induced cytokine release syndrome in kidney graft recipients. It seems likely that recombinant proteins with increasingly effective suppression of specific elements of the immune response will become an essential element in clinical protocols.

Abatacept↗

PubMed1994

The cyclic adenosine 3',5'-monophosphate- and the glucocorticoid-dependent enhancers are targets for insulin repression of tyrosine aminotransferase gene transcription.

The pathway of gluconeogenesis is activated in liver shortly after birth and is controlled by glucagon and glucocorticoids, which stimulate, and insulin, which inhibits, the expression of genes coding for gluconeogenic enzymes. To understand the molecular basis of this cell type-specific and coordinate control, we analyzed the cis-regulatory elements of the tyrosine aminotransferase gene, which confer liver cell-specific expression in dependence of these hormones. The cAMP-responsive element (CRE) of the TAT gene is an essential element within a liver-specific enhancer and is recognized by the CRE-binding protein (CREB) in a phosphorylation-dependent manner. The glucocorticoid response is mediated by a complex regulatory unit comprised of the glucocorticoid receptor and other transcription factor-binding sites. Here, we show that both the cAMP- and glucocorticoid-inducible enhancers are targets for the antagonistic effects of insulin. The insulin-responsive sequences coincide with the CREB-binding site of the cAMP-responsive enhancer and a hepatocyte nuclear factor-3-binding site within the glucocorticoid-responsive unit. This design of the hormone-dependent enhancers reflects the molecular mechanism underlying the onset of tyrosine aminotransferase expression at birth when insulin levels decrease and concentrations of glucagon and glucocorticoids increase.

Animals↗

PubMed2002

In vitro activity of cefazoline and cefuroxime in presence of essential and trace elements.

Present research focuses to evaluate changes in antimicrobial activity of cefazolin sodium and cefuroxime after interactions with essential and trace elements. The minimum inhibitory concentration (MIC) was observed and subsequently compared with the standard MIC's of the respective drug by agar dilution method against a variety of Gram positive and Gram negative organisms. It was observed that these metal elements are essential for our body, either present within the body or co-administered with vitamins or otherwise, markedly influence the MIC's of antibiotics by producing synergism or antagonism.

Journal Article↗

PubMed1987

Uptake and toxic effects of heavy metal ions: interactions among cadmium, copper and zinc in cultured cells.

Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements. The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.

Animals↗

PubMed1989

Microprobe analysis of element distribution in bovine extracellular matrices and muscle.

The concentrations of some essential elements, Na, K, P, S and Cl were determined by microprobe analysis in bovine extracellular matrices of cartilage, tendon and elastic tissue (ligamentum nuchae) and in muscle cells. The values for the different tissues were compared and related to the blood electrolyte concentrations. Among the connective tissues the highest Na and lowest Cl values were found for cartilage which bears a high negative charge. The lowest concentrations of these elements occurred in elastic tissue which is relatively non-polar. In the three extracellular matrices sodium levels exceeded potassium. In myofibers potassium was the major cation at 30 times the blood value and about 3 times the concentration of sodium. Chlorine values were around 0.4 that of blood. Sulfur and phosphorus are components of the tissue macromolecules. The negative charge on the extracellular matrices is a function of carboxyl and sulfate radicals. In the myofiber this property is largely attributable to carboxyl and phosphate groups. Differences in potassium-sodium distribution in cells and extracellular matrices are attributed partly to the microtrabecular lattice and to the ordered state of cell water. In general the element concentrations and selective distribution can be related to the chemical composition and organization of the tissue, the net immobile charge, the nature of the dispersion medium (water) and changes in its dielectric constant, and to the physico-chemical properties of the individual ions.

Animals↗

PubMed1999

Proximal promoter of the rat brain creatine kinase gene lacks a consensus CRE element but is essential for the cAMP-mediated increased transcription in glioblastoma cells.

Our previous studies have shown that transcription of brain creatine kinase (CKB) mRNA in U87-MG glioblastoma cells is stimulated by a forskolin-mediated increase in cyclic AMP (cAMP) via a pathway involving protein kinase A (PKA) and the activation of Galphas proteins. In this report, we have employed transient transfection to investigate the rat CKB gene elements essential for the cAMP-mediated induction of rat CKB transcription in human U87 cells and have mapped the transcription start site of the induced CKB transcripts. We found that the level of induced transcription from the transfected genomic rat CKB gene was the same whether transcription was driven by 2.9 kb of CKB promoter plus 5' flanking sequence or the 0.2 kb CKB promoter, suggesting that the proximal CKB promoter was essential. Also, the level of induced transcription of the chloramphenicol acetyl transferase (CAT) reporter gene driven by the 2.9 kb CKB promoter was the same as with the 0.2 kb CKB promoter. Analyses of a series of 5' deletions of the 0.2 kb proximal CKB promoter showed that the sequences between -80 bp and +1 bp were essential for the cAMP-mediated induction of CKB transcription, despite the absence of a consensus cAMP response element (CRE) sequence in that region. In agreement, gel mobility shift assays showed that nuclear extracts from U87 cells contained a protein(s) which bound specifically to a [32P]CKB DNA probe containing the -60 bp to +1 bp sequence. Mapping the 5' end of the CKB transcripts showed that the initiation of the cAMP-induced transcription occurred almost exclusively from the downstream transcription start site, apparently under the initiation direction of the nonconsensus (-28) TTAA element and not the consensus (-60) TATAAATA element. The results are discussed with regard to nuclear protein factors which may be involved, and the possible cAMP-mediated increase in CKB transcription during myelinogenesis, since the differentiation of oligodendrocytes has previously been shown to be accelerated by increased intracellular cAMP.

1-Methyl-3-isobutylxanthine↗

PubMed1996

ORE, a eukaryotic minimal essential osmotic response element. The aldose reductase gene in hyperosmotic stress.

Organisms, almost universally, adapt to hyperosmotic stress through increased accumulation of organic osmolytes but the molecular mechanisms have only begun to be addressed. Among mammalian tissues, renal medullary cells are uniquely exposed to extreme hyperosmotic stress. Sorbitol, synthesized through aldose reductase, is a predominant osmolyte induced under hyperosmotic conditions in renal cells. Using a rabbit renal cell line, we originally demonstrated that hyperosmotic stress induces transcription of the aldose reductase gene. Recently, we cloned the rabbit aldose reductase gene, characterized its structure, and found the first evidence of an osmotic response region in a eukaryotic gene. Now, we have progressively subdivided this 3221-base pair (bp) region into discrete fragments in reporter gene constructs. Thereby, we have functionally defined the smallest sequence able to confer hyperosmotic response on a downstream gene independent of other putative cis-elements, that is, a minimal essential osmotic response element (ORE). The sequence of the ORE is CGGAAAATCAC(C) (bp -1105/-1094). A 17-bp fragment (-1108/-1092) containing the ORE used as a probe in electrophoretic mobility shift assays suggests hyperosmotic induction of a slowly migrating band. Isolation of trans-acting factor(s) and characterization of their interaction with the ORE should elucidate the basic mechanisms for regulation of gene expression by hyperosmotic stress.

Aldehyde Reductase↗

PubMed1976

An in vitro study of bacterial response to inert and reactive metals and to methyl methacrylate.

The clinical use of inert materials for internal fixation and joint replacement devices is increasing rapidly; studies on the effect of these materials on bacteria and host resistance to infection have not kept apace. Any substance placed within the body may interfere with host-parasite interaction, either by its physical presence or by physiochemical activity at its interface with the surrounding tissue. Either mechanism, by altering the normal host defense mechanism, may promote or retard bacterial growth. Bacterial growth may also be altered if a trace element essential to or inhibitory to the bacteria or an element that antagonizes or potentiates humoral antibacterial systems is leached from the substance. We have tested bacterial growth and inhibition in vitro in the presence of substances used as implant materials: surgical silver, iron, zinc-coated galvanized iron, aluminum alloy, stainless steel, Vitallium, and methyl methacrylate. Our results showed: 1) metals that have low grades of tissue reactivity and little bacteriotoxic effect provided a framework along which bacterial growth and propagation occurred; 2) metals that have higher levels of cellular reactivity, specifically aluminum and galvanized wire, caused selective bacterial toxicity. The in vitro response of bacteria to methyl methacrylate was similar to that of Vitallium and other inert substances, i.e., growth and propagation were abundant adjacent to methyl methacrylate. These studies led us to speculate that, if similar phenomena occur in vivo, bacterial growth and dissemination might be increased when an inert implant material was used and decreased when the implant material was more reactive.

Bacteria↗

PubMed2002

The involvement of molybdenum in life.

Quite extraordinarily molybdenum is an essential element in life for the uptake of nitrogen from both nitrogen gas and nitrate, yet it is a relatively rare heavy trace element. It also functions in a few extremely important oxygen-atom transfer reactions at low redox potential. This review poses the question "Why does life depend upon molybdenum?" The answer has to be based upon the availability of the element and on chemical superiority in carrying out the essential tasks. We illustrate here the peculiarities of molybdenum chemistry and how they have become part of certain enzymes. The uptake and incorporation of molybdenum are dependent on its availability, selective pumps, and carriers (chaperones), but 4.5 x 10(9) years ago molybdenum was not available when both tungsten and vanadium or even iron were possibly used in its place. While these possibilities are explored, they leave many unanswered questions concerning the selection today of molybdenum.

Animals↗

PubMed2005

Adult valvular heart disease: a practical approach.

The diagnosis and management of valvular heart disease is an important element of primary care practice. This article reviews the essential elements of four common valvular disorders, including signs and symptoms. The disorders reviewed are aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation. The article places an emphasis on practical aspects of care.

Adult↗

PubMed1992

Growth hormone actions on fat distribution and metabolism.

The secretion of growth hormone (GH) and the mass and distribution of body fat are linked through a complex series of interactions. There is increasing evidence that a GH/fat cycle exists and that elements of this cycle may possess regulatory functions. The essential elements of the cycle are: (1) GH-deficient individuals are often obese and lose body fat when they are treated; GH is lipolytic in vitro and causes an acute release of free fatty acids (FFA) when administered in vivo; (3) circulating FFA inhibit the pituitary release of GH by most secretagogues, including growth hormone releasing hormone, and (4) the obese state is characterized by a defect in GH release which can be reversed by weight loss.

Adipose Tissue↗

PubMed2005

[Features of homeostasis in surgeons].

The article deals with results of studies concerning homeostasis system in surgeons working in major industrial city. Findings are disorders of elements balance, that manifest through lower content of some essential elements and accumulation of toxic ones. The authors defined correlations between adaptational level, immunologic and elemental states of the body.

Adaptation, Physiological↗

PubMed2005

Selenium, a versatile trace element: current research implications.

Selenium (Se), a trace element, has evolved from its toxic properties to an essential element. Se was known a potent antioxidant through glutathione peroxidase (selenium being part of this molecule). Later, many other selenium-binding proteins were discovered and their functions were tried to be known with unsuccessful results in many cases. Se is known to be involved in carcinogenesis, immune function, male reproduction, cardiovascular diseases etc. The specific mechanism of the involvement of the element is still not known. Recent research with application of modern research tools viz. bioinformatics, cDNA microarray and transgenesis have revealed the mechanism of selenium involvement in various processes. This review highlights mysterious and useful roles of selenium in biological processes.

Animals↗

PubMed1983

Trace elements and blood pressure.

Essential trace elements such as zinc, iron, and copper participate in various enzyme reactions directly related to the regulation of blood pressure and indirectly related to generation of oxidative metabolic energy, alterations in blood lipid levels, and alterations in taste acuity. The toxicological action of several heavy metal ions including cadmium, lead, mercury, and thallium can cause hypertension by affecting hormone metabolism, vasoconstriction, and renal tubular function. We conclude, however, that neither deficiencies of essential elements nor the presence of toxic heavy metals are primary causes of hypertension in our population.

Animals↗

PubMed2001

Effects of ionic valency of interacting metal elements in ion uptake by carrot (Daucas carota cv. U.S. harumakigosun).

Interaction of elements in the course of element uptake by carrot (Daucas carota cv. U.S. harumakigosun) exerted by the addition of elements, such as Rb, Zn, and Al, was investigated. For the purpose of precise evaluation of uptake behavior, the simultaneous determination of absorption of Na, Be, Sr, Mn, Co, Zn, Ce, Pm, and Gd was conducted by the multitracer technique. For root uptakes, Al exhibited its influence on the uptake of essential elements and on the uptake of toxic or unbeneficial ones, presumably as a result of the large electric valency that caused cell membrane disintegrity. On the other hand, Zn as a divalent cation only affected the uptake of essential and beneficial elements. Rubidium, which is a monovalent cation, did not exhibit any effect on the uptake of other ions. Concerning shoot uptakes, inhibition by Zn and Al, but not by Rb, was observed for the uptake of Sr, Mn, Co, and Zn. From the present investigation, it is suggested that there exists an interaction between added ions and the elements taken into plants and that the degree of interaction increases in the increasing order of ionic valency: M+ (Rb), M2+ (Zn), and M3+ (Al).

Aluminum↗