Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43026 (
lipopolysaccharide
)
62,215
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Inductively coupled plasma emission spectroscopy was used to quantitate the metal cations bound to outer and cytoplasmic membranes and to extracted
lipopolysaccharide
from several Escherichia coli K12 strains. The outer membrane was found to be enriched in both calcium and magnesium relative to the cytoplasmic membrane. Both membranes contained significant levels of iron, aluminum, and
zinc
. The multivalent cation content of the
lipopolysaccharide
resembled that of the intact outer membrane. Lipopolysaccharide extracted from wild-type k12 strains contained higher levels of Mg than Ca regardless of the growth medium, but the medium used for growth did affect the relative amounts of bound Mg as well as the levels of the minor cations iron, aluminum, and
zinc
. In contrast,
lipopolysaccharide
isolated from a deep rough mutant strain, D21f2, contained more Ca than Mg. Electrodialysis of
lipopolysaccharide
from wild-type k12 strains removed 1 mol of Mg per mol of
lipopolysaccharide
but did not significantly affect the level of other bound metal ions. Dialysis of
lipopolysaccharide
against sodium (ethylenedinitrilo)tetraacetate removed most of the Mg and Ca, resulting in a sodium salt. The equimolar replacement of divalent cations with sodium in the sodium salt resulted in a net loss of counterion change. The sodium salt was dialyzed against either tris(hydroxymethyl)aminomethane hydrochloride, CaCl2, MgCl2, or TbCl3, and the resulting
lipopolysaccharide
salts were analyzed for their ionic composition. It was shown that tris(hydroxymethyl)aminomethane and Ca can replace some but not all of the Na bound to the sodium salt, but all of the other multivalent cations tested replaced Na, resulting in uniform
lipopolysaccharide
salts. Lipopolysaccharide isolated from the deep rough mutant strain D21f2 was also converted into a sodium salt. Relative to the wild-type
lipopolysaccharide
, Na was able to neutralize the anionic charge to a greater extent in the mutant
lipopolysaccharide
. Our results suggest that the loss of specific groups in the core region of the
lipopolysaccharide
from the mutant strain results in a more open structure that allows the binding of larger cations and of more monovalent cations.
...
PMID:Quantitation of metal cations bound to membranes and extracted lipopolysaccharide of Escherichia coli. 634 72
In goats with trypanosomiasis (T. vivax or T. congolense) no marked fall in plasma
zinc
concentration was seen despite high temperature peaks, whereas plasma concentrations of iron tended to undergo some decline. In goats infected with Ehrlichia phagocytophila, there was a marked decline in plasma
zinc
and iron to low values on the 3rd and 4th day, respectively. Circulating endogenous pyrogen (EP) or leukocytic endogenous mediator (LEM) could not be detected in plasma from febrile goats with tick-borne fever. The intravenous injection of leukocytic pyrogen (LP) in kids caused characteristic monophasic febrile reactions, whereas no significant changes in plasma trace metals were found. So, previous evidence purporting to show that LP is similar to or may be identical with LEM is demonstrably inconclusive. Intravenous injection of E. coli
lipopolysaccharide
(
LPS
) or staphylococcal enterotoxin B (SEB) induced fever and lowering of plasma
zinc
and iron concentrations. The decrease in those trace metal values was more persistent in goats given SEB than in those given E. coli
LPS
. After intramammary infusion of SEB or E. coli
LPS
, fever and significant decreases in plasma
zinc
and iron concentrations were observed but no clear relationship was found between the temperature responses and the alterations in plasma trace metal concentrations. Furthermore, the decrease in plasma iron concentration developed more rapidly in goats given SEB than in those given E. coli
LPS
, whereas the decrease in plasma
zinc
concentrations in the former was more delayed. These data support the theory that the concentrations of
zinc
and iron in plasma are regulated by different mechanisms, whereas febrile reactions are mediated by another type of endogenous protein.
...
PMID:Fever and changes in plasma zinc and iron concentrations in the goat: the role of leukocytic pyrogen. 639 59
The influence of
zinc
on the in vitro antibody response to antigen or mitogen stimulation was studied by adding various concentrations of ZnCl2 to cultures of spleen cells stimulated with sheep erythrocytes, trinitrophenyl-
lipopolysaccharide
or with the polyclonal B cell activator E. coli
lipopolysaccharide
(
LPS
). Addition of ZnCl2 in concentrations ranging from 10(-8) or 10(-7) to 10(-5) M increased the specific antibody response to antigens or the polyclonal antibody synthesis induced by stimulation with
LPS
, when the response of the assayed population in the control cultures without ZnCl2 was low, as observed in cultures without 2-mercaptoethanol (2-ME). However, in cultures supplemented with 2-ME, the potentiating effect of ZnCl2 diminished or disappeared or even the antibody response was inhibited. Higher concentrations of ZnCl2 markedly depressed (5 X 10(-5) M) or abolished (10(-4)) the in vitro induced antibody response in all cultures. The various mechanisms which could mediate the effects of
zinc
are discussed.
...
PMID:Modulation by zinc of the in vitro antibody response to T-dependent and T-independent antigens. 660 99
The effects of varied levels of maternal dietary
zinc
on growth and immunological development of suckling A/J mice were studied. From 5 days postpartum, lactating dams were fed biotin-fortified egg-white diets containing the following levels of
zinc
: 1.6 microgram/g (low
zinc
), 3.6 microgram/g (intermediate
zinc
), 5.8 microgram/g (moderate
zinc
) and 30 microgram/g (control). At 17 days of age, low
zinc
pups exhibited reduced body weight gain (70%), smaller thymuses and spleens, and reduced splenocyte numbers (18%). Intermediate
zinc
pups had normal body weights but slightly reduced spleens and thymuses; moderate
zinc
pups were unaffected. Since suckling mice are not fully immunocompetent, splenic mitogenic responses to phytohemagglutinin (PHA), concanavalin A (Con A),
lipopolysaccharide
(
LPS
), pokeweed mitogen (PWM), and dextran sulfate (Dx) were used to evaluate the status of various lymphocyte subpopulations. Neonates from the low
zinc
group gave no Con A response and limited responses to
LPS
and PWM (50%). Intermediate
zinc
pups responded satisfactorily to all mitogens except
LPS
(64%); moderate
zinc
pups responded normally. It was concluded that 5.8 microgram/g maternal dietary
zinc
, fed day 5-17 postpartum, is adequate for normal neonatal growth and mitogenic responses. Conversely, 1.6 microgram Zn/g caused neonatal growth retardation and reduced mitogenic responses without excessive mortality.
...
PMID:Effect of maternal dietary zinc on growth and mitogenic responsiveness in suckling mice. 711 95
Metallothioneins (MTs) are sulfhydryl-rich proteins. MT-I and MT-II are found in all tissues of the body, while MT-III exists only in brain. Regulation of MT-I and MT-III mRNA was studied in brain and liver of control C57BL/6J mice and mice given chemicals known to increase MT-I, namely,
lipopolysaccharide
(
LPS
),
zinc
chloride (Zn), cadmium chloride (Cd), dexamethasone (Dex), ethanol, and kainic acid (KA). Northern blot analysis revealed that MT-I mRNA levels in liver were induced dramatically (12-27-fold over basal levels) by all of the chemicals, while in brain only
LPS
produced an increase in MT-I mRNA (2-fold). Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30%. Because brain is such a heterogenous tissue, in situ hybridization was used to localize MT-I and MT-III mRNA in control and treated mice. MT-I mRNA signal, which was most abundant in the glial cells of the Purkinje cell layer of the cerebellum in control mice, appeared to be enhanced in mice given the MT-I inducers (
LPS
, Zn, Cd, Dex, ethanol, and KA). MT-I mRNA hybridization signal was also enhanced in the olfactory bulbs from
LPS
- and Cd-treated mice, while this signal was present but weak in control brains. MT-III mRNA hybridization signals were localized in hippocampus and co-localized with MT-I message in the glial cells of the Purkinje cell layer of the cerebellum. In addition, diffuse MT-III mRNA signals were visible in areas of the cerebral cortex, and in the molecular layer of the cerebellum. Signals for MT-III in hippocampus appeared to be reduced by KA, Dex and
LPS
treatment, while in the cortical region, MT-III mRNA signals appeared to be enhanced by KA, Cd, and ethanol treatment. In conclusion, both MT-I and MT-III expression in brain appears to be modulated by exogenous treatment, however, the changes are small in relation to those observed in liver. Chemical-induced alterations of MT mRNA are non-uniform throughout the brain, and thus best studied in a region-specific manner.
...
PMID:Chemical modulation of metallothionein I and III mRNA in mouse brain. 765 47
In search for a rational way to convert the information encoded in peptide structures into peptidomimetics, major progress could be made by coupling the power of selection methods, now enormously increased in number as a result of the development of combinatorial peptide libraries, with the rational design of structure-inducing templates for the selectable sequences. The availability of libraries of peptides with predetermined structure would enable selection-driven peptidomimetic design, whereby a conformational model for the peptide pharmacophore would be directly derived from the screening, allowing the design of a suitable non-peptidic scaffold to replace the peptide backbone. We describe here the first example of a conformationally homogeneous combinatorial peptide library, which yields ligands with the expected structure upon selection. The library was built by randomising five positions in the alpha-helical portion of a 26 amino acid Cys2His2 consensus "zinc-finger" motif. Since in
zinc
-fingers metal coordination and folding are coupled, in our library metal-dependent binding represents a built-in control against the selection of structurally undefined sequences. The alpha-helical library was produced as both fusion with the pVIII protein of filamentous phage and soluble peptides by chemical synthesis, the latter enabling the expansion of the selectable repertoire by the inclusion of non-coded amino acids. The two libraries were independently screened with the same receptor (a monoclonal IgA reactive against the
lipopolysaccharide
of the human pathogen Shigella flexneri), yielding a very similar consensus. In particular, the peptides defined by both methods showed very strong,
zinc
-dependent binding to the IgA. The geometrical arrangement of the side-chains of the selected peptide pharmacophore was shown by circular dichroism, Co(II)-complex absorption and high-resolution NMR to be structurally invariant with respect to the parent
zinc
-finger.
...
PMID:A conformationally homogeneous combinatorial peptide library. 770 66
The titers of serum antibodies to natural infection with enteric and respiratory pathogens, to a food antigen and to tetanus and diphtheria toxoid were evaluated by enzyme-linked immunosorbent assay in 1,554 Ecuadorian children younger than 5 years of age. The nutritional status of the children was assessed by anthropometry and measurement of biochemical status indicators. The children were enrolled in a representative national nutrition and health survey. Antibody titers were analyzed as a function of the nutritional status of the children. For 12 of 14 antibody concentrations tested, underweight children showed lower antibody titers than did control children. The difference was statistically significant for antibody to both T-cell-dependent antigens (tetanus toxoid, rotavirus, respiratory syncytial virus) and T-cell-independent antigens (
lipopolysaccharide
, polyribosyl-ribitol phosphate, capsular polysaccharide). When children with a recent episode of diarrhea were excluded, many of the differences remained significant. When these children were further classified by age, only difference in titers of antibodies to respiratory syncytial virus and tetanus toxoid remained significant. No statistically significant difference was detected between underweight and control children with respect to protective antibody levels to four bacterial antigens. Anemic children showed significantly lower antibody levels to both T-cell-dependent and T-cell-independent antigens than did control children, and a higher proportion of anemic children had diphtheria antitoxin below a conservatively defined protective antibody level. No major differences in antibody titers were seen between children with different retinol and
zinc
concentrations in serum.
...
PMID:Effect of malnutrition in Ecuadorian children on titers of serum antibodies to various microbial antigens. 771 15
Zinc
is known to be greatly involved in the regulation of immune functions. Pharmacological
zinc
supplementation, leading to serum
zinc
concentrations of more than 0.025 mM, has often been suggested to improve immune responses. However, the exact influence of elevated
zinc
level on immune functions has not yet been investigated. We found that
zinc
level selectively enhances cytokine induction by
lipopolysaccharide
(
LPS
) in a concentration-dependent fashion: as little as 0.0125 mM supplemental
zinc
led to nearly 50% elevated interleukin-1 beta (IL-1 beta) levels both in polymorphonuclear cells (PBMC) and whole-blood cultures. The secretion of interferon-gamma (IFN-gamma) could be increased more than 10-fold by 0.1 mM
zinc
. This could not be observed during stimulation with phytohaemagglutin (PHA). In contrast,
zinc
levels concentration-dependently down-regulated monocyte activation caused by the superantigens, staphylococcal enterotoxins A and E (SEA, SEE, more than 90% down-regulation by 0.1 mM
zinc
), the Mycoplasma arthritidis-derived superantigen (MAS), but not toxic shock syndrome toxin-1 (TSST-1), while T-cell response remained unaffected. This was not the result of chemical degradation of the superantigens. We assume that
zinc
concentration regulates interactions between SEA, SEE and MAS, but not TSST-1 and their major histocompatibility complex (MHC) class II-binding sites. Our data demonstrate that
zinc
levels control the secretion of IFN-gamma and monokines after both
LPS
and superantigen challenge within a clinically relevant range of concentrations. This reveals new perspectives and indications for
zinc
supplementation and also indicates potential risks of therapeutic application of
zinc
.
...
PMID:Zinc regulates cytokine induction by superantigens and lipopolysaccharide. 775 Oct 4
Measurement of cytokine secretion in vitro is usually performed in culture medium supplemented with human serum. We compared the secretion of interferon-gamma and interleukin-1 beta as a parameter for lymphocyte and monocyte activation in RPMI 1640 medium supplemented with fetal calf or autologous serum in serum-free medium and protein-free medium. Four different stimulatory mechanisms were tested: phytohemagglutinin, toxic shock syndrome toxin-1 (TSST-1),
lipopolysaccharide
(
LPS
), and
zinc
ions. We found that the optimal stimulatory
zinc
concentration depended on the total protein content of the medium, whereas the monokine levels were dependent on the concentration of transport proteins such as transferrin. Monokine induction by
LPS
or TSST-1 were each influenced by the protein and serum composition in a specific manner. Our results show that the differing mechanisms of cytokine induction are influenced by the medium and serum composition in a diverse but specific manner. Serum- or protein-free medium are especially suitable after superantigen challenge when
LPS
activity needs to be ruled out or after activation by agents with only a weak stimulatory capacity.
...
PMID:Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide-induced production of IFN-gamma and IL-1 beta by human mononuclear cells. 779 Jul 74
Zinc
is essential for immunologic function; therefore, it has been postulated that elevated serum levels of
zinc
might lead to improved immune responses. However, it is not known whether or how serum
zinc
levels contribute to a clinically relevant mechanism of immunologic activation. In our studies with human peripheral blood mononuclear cells and whole blood, the
zinc
level selectively enhanced the biologic activity of endotoxin. The combination of nonstimulatory doses of
lipopolysaccharide
(
LPS
) and nonstimulatory concentrations of
zinc
led to the secretion of large amounts of interleukin (IL)-1 beta. In contrast,
zinc
levels specifically down-regulated monocyte activation caused by some superantigens, staphylococcal enterotoxin A and E and Mycoplasma arthritidis--derived superantigen, but not toxic shock syndrome toxin-1. This demonstrates that
zinc
levels control IL-1 beta secretion after both
LPS
and superantigen challenge within a clinically relevant range of concentrations. Our data suggest that the indications and contraindications for clinical
zinc
supplementation should be reconsidered.
...
PMID:Divergent effects of zinc on different bacterial pathogenic agents. 784 97
<< Previous
1
2
3
4
5
6
7
8
9
10
Next >>