SEARCH · PubMed Health

Results for “Dextrans”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1977

Mechanisms of B cell tolerance. I. Tolerance to dextran B1355 induced with the oxidized dextran.

The bacterial dextran B1355, which is normally a potent thymus-independent immunogen, was made tolerogenic by oxidation. The injection of the oxidized dextran into BALB/c mice before, at the same time, or up to 4 days after the injection of the immunogenic form of the dextran resulted in a marked immunologically specific suppression of the number of anti-dextran antibody-forming cells found in the spleen. This suppression resulted from a direct inactivation of antibody-forming cell precursors rather than from either inhibition of antibody secretion or the exhaustive utilization of precursor B cells that have been observed in other tolerance systems. A substantial degree of tolerance was achieved after only a 1-hr in vivo exposure of the spleen cells to the tolerogen. At a dose of 1 mg of oxidized dextran per mouse, tolerance persised for at least 3 weeks. A complete recovery was apparent by 10 weeks. The stability of the tolerance was demonstrated by transferring tolerant spleen cells to irradiated recipients. The response in the recipient animals to an immunogenic dextran challenge remained suppressed. It appears that the tolerogenicity of the oxidized dextran is due to its ability to couple covalently with free amino groups in or near the receptor site of the cell membrane via the reactive dialdehyde groups of the dextran.

Animals↗

PubMed1996

The anti-Dextran response of scid mice transgenic for the heavy chain of a Dextran specific IgM antibody.

Mice homozygous for the scid mutation bear a severe defect in their ability to rearrange V(D)J gene segments to yield active genes for immunoglobulin and T cell receptor molecules. In older animals few clones of B and T cells can arise at random, a phenomenon called leakyness of the scid mutation. We established scid mice carrying as a transgene the rearranged heavy chain of the IgM/lambda1 antibody MOPC 104E with specificity for the alpha(1,3) glucosidic linkages in Dextran. Despite the scid defect one-third of these mice immunized with the thymus independent antigen Dextran at 2 weeks of age, and all of those immunized at 6 weeks responded with anti-Dextran antibodies bearing the lambda light chain. This indicates that despite the scid mutation these animals had at least once successfully rearranged their endogenous lambda1 light chain gene segments and harbor Dextran specific B cells. These mice thus provided for the first time the opportunity to study the immune response of B cells of a single specificity in an environment that should, as we shall argue, be devoid of regulatory B and T cells able to recognize the idiotype of the responding cells. One week after immunization the anti-Dextran response of 5- to 6-week-old mu-transgenic scid mice amounted to 30% of the response of mu-transgenic non-scid mice but in essence both responses followed the same kinetics, reaching antibody concentrations indistinguishable from each other 8 weeks after a single dose of Dextran. Furthermore, the ready response of young mu-transgenic scid mice to this antigen by employment of endogenously rearranged lambda1 light chains allowed experiments to be done to compare the frequency of lambda1 light chain rearrangements in mu-transgenic scid mice to that in mu-transgenic non-scid mice. This was done in limiting dilution assays counting B cell precursors responsive to mitogen and differentiating in vitro to produce antibodies toward Dextran. Specific precursors were reduced to about 1% in the spleen of mu-transgenic scid mice when compared to the spleen of mu-transgenic non-scid mice; those in the peritoneal cavity lymphocyte population were reduced to about 12%.

Animals↗

PubMed1980

The influence of trauma, Dextran 1000, and Dextran 40 on the lodgement of circulating tumor cells.

Earlier studies have shown that trauma and infusion of Dextran 1000 increased the formation of pulmonary metastases after i.v. tumor cell injection in rats. Infusion of Dextran 40 enhanced the pulmonary metastasis formation in traumatized but not in non-traumatized animals. In this study tumor cells labelled with a radioactive isotope were used to register the lodgement circulating tumor cells after trauma and infusion of Dextran 1000 and Dextran 40. It was found that the pulmonary lodgement of tumor cells was increased after trauma and infusion of Dextran 1000. Dextran 40 did not influence the lodgement in a significant way either in normal or in traumatized animals. Thus, the increased formation of metastases after trauma and infusion of Dextran 1000 seems to depend upon an increased tumor cell lodgement.

Animals↗

PubMed2005

Dextran dextrinase and dextran of Gluconobacter oxydans.

Certain strains of Gluconobacter oxydans have been known since the 1940s to produce the enzyme dextran dextrinase (DDase; EC2.4.1.2)-a transglucosidase converting maltodextrins into (oligo)dextran. The enzyme catalyses the transfer of an alpha1,4 linked glucosyl unit from a donor to an acceptor molecule, forming an alpha1,6 linkage: consecutive glucosyl transfers result in the formation of high molecular weight dextran from maltodextrins. In the early 1990s, the group of K. Yamamoto in Japan revived research on DDase, focussing on the purification and characterisation of the intracellular DDase produced by G. oxydans ATCC 11894. More recently, this was taken further by Y. Suzuki and coworkers, who investigated the properties and kinetics of the extracellular DDase formed by the same strain. Our group further elaborated on fermentation processes to optimise DDase production and dextran formation, DDase characterisation and its use as a biocatalyst, and the physiological link between intracellular and extracellular DDase. Here, we present a condensed overview of the current scientific status and the application potential of G. oxydans DDase and its products, (oligo)dextrans. The production of DDase as well as of dextran is first described via optimised fermentation processes. Specific assays for measuring DDase activity are also outlined. The general characteristics, substrate specificity, and mode of action of DDase as a transglucosidase are described in detail. Two forms of DDase are produced by G. oxydans depending on nutritional fermentation conditions: an intracellular and an extracellular form. The relationship between the two enzyme forms is also discussed. Furthermore, applications of DDase, e.g. production of (oligo)dextran, transglucosylated products and speciality oligosaccharides, are summarized.

Biotechnology↗

PubMed1978

Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes.

Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.

Aging↗

PubMed1990

Anti-human immunodeficiency virus effects of dextran sulfate are strain dependent and synergistic or antagonistic when dextran sulfate is given in combination with dideoxynucleosides.

The effects of three molecular weight ranges of dextran sulfate on five different human immunodeficiency virus (HIV) isolates (from patients with acquired immunodeficiency syndrome), alone and in combination with dideoxynucleosides, were investigated in vitro. The higher the molecular weight range of dextran sulfate, the more potent the activity as assessed by a quantitative syncytium formation assay. Although all five HIV isolates had similar susceptibilities to the inhibitory effects of dideoxynucleosides, the two clinical isolates of HIV (HIV type 1 [HIV-1] TM and SP) exhibited a pattern of reduced susceptibility to dextran sulfate when compared with the two cloned isolates (HIV-1 WMF and HIV-2 ROD) and a prototype laboratory strain (HIV-1 IIIB). In combination with dideoxynucleosides, the high-molecular-weight range of dextran sulfate (500,000) resulted in an antagonistic response directed against the two clinical isolates of HIV (HIV-1 TM and SP) when the antiviral concentrations of dextran sulfate were in the ineffective range. Additive or synergistic effects were seen with the other three HIV isolates and all five HIV isolates when the low-molecular-weight range of dextran sulfate (8,000) was used. The results of these studies raise issues on the impact of drug-resistant strains on disease progression and the use of dextran sulfate in combination with nucleoside analogs for the clinical management of HIV disease.

Cells, Cultured↗

PubMed1976

Permeability of renal peritubular capillaries to neutral dextrans dextrans and endogenous albumin.

Renal lymph-to-renal vein concentration ratios (CL/CV) for neutral dextrans (18-42 A effective radii) and endogenous serum albumin were measured in rats before and during acute colume expansion with isoncotic plasma or Ringer solution. Under all conditions studied, CL/CV decreased with increasing dextran size, in normal hydropenia falling from 0.93 +/- 0.03 SE at 18 A to 0.24 +/- 0.02 a 42 A (n = 12). Albumin (36 A pradius) behaved in a manner similar to a 40 A dextran, CL/CV averaging 0.33 +/- 0.03 (n = 12) in hydropenia. For all dextran sizes studied and for albumin, CL/CV decreased markedly during either form of volume expansion. Ringer loading produced significantly greater decreases in CL/CV for the larger dextrans and albumin than did plasma loading, and also resulted in much greater increases in renal lymph flow, while causing increases in whole kidney fluid reabsorption similar to those with plasma loading. With a compartmental model in which diffusion of dextrans and albumin from capillary lumen to interstitium is opposed by capillary uptake of tubule reabsorbate, these results are interpreted to indicate that connective reflection coefficients for dextrans with radii great than or equal to 36 A and albumin are essentially equal to 1. Indirect evidence is therefore provided that albumin and the larger globulins exert their full osmotic pressures across the walls of peritubular capillaries.

Animals↗

PubMed1983

Electron microscopy of cultured human corneas. Osmotic hydration and the use of a dextran fraction (dextran T 500) in organ culture.

Human corneas were studied by means of electron microscopy after culture at 31 degrees C for two to 20 days in a medium containing 8% dextran T 500. Dextran T 500, a strong osmotic agent, was included in the culture medium to prevent excessive swelling of the cornea. In order to exclude the possibility that the observed effects were the result of osmotic changes during fixation, in each experiment, fixatives with different osmolalities were used (430, 574, 727, and 812 mOsm). After 8, 16, and 20 days of culture, vacuoles appeared that were filled with dextran; the cytoplasm was completely filled with these vacuoles. The vacuolization was not limited to the endothelium, but was also observed in stromal keratocytes and to a limited extent in the epithelium. It was concluded that the monolayer of endothelium was still intact after 20 days of culture in medium containing 8% dextran T 500, and, secondly, that the dextran might have been taken up by endocytosis. Whether or not the uptake of dextran has a long-term toxic effect on the corneal cells remains to be elucidated.

Adolescent↗

PubMed1983

Effect of dextran and dextran modifications on the thermal and proteolytic stability of conjugated bovine testis beta-galactosidase and human serum albumin.

In order to study carbohydrate-induced protein stabilization bovine testis beta-galactosidase and human serum albumin were conjugated with dextran, partially acetylated dextran and partially methylated dextran. The conjugates and the free proteins were compared with respect to thermal stability at 50 degrees C and resistance to proteolytic digestion by subtilopeptidase A. Both beta-galactosidase and serum albumin were stabilized by conjugation with polysaccharide. However, higher stability was achieved by conjugating the proteins with the hydrophilic polysaccharides, dextran and acetylated dextran, than by conjugation with the hydrophobic polysaccharide, methylated dextran. The results are discussed in relation to possible explanations of carbohydrate-induced protein stabilization.

Animals↗

PubMed2000

Toxicity and DNA binding of dextran-doxorubicin conjugates in multidrug-resistant KB-V1 cells: optimization of dextran size.

We previously showed that conjugating doxorubicin to very large 70-500 kDa dextran decreased its removal rate from P-glycoprotein (P-gp) over-expressing, multidrug-resistant KB-V1 cells. Furthermore these conjugates could act synergistically with other cancer drugs. In the drug-sensitive 3-1 clone, but not in the V1 subclone which was 300-fold more resistant to free doxorubicin, conjugation led to a size-related decrease in toxicity. Here we identified the optimal size of dextran for avoiding P-gp-mediated efflux and yet preserving as much as possible doxorubicin toxicity. Chemically reduced, intracellularly stable 3.4-10 kDa conjugates were prepared. Confocal microscopy and fluorescence quenching experiments showed that these conjugates entered nuclei and interacted with DNA. In 3-1 cells, but not in V1 cells, cytotoxicity of conjugates decreased 14- to 45-fold linearly related to log size of the carrier (r=0.95). In V1 cells toxicity of the 10 kDa conjugate exceeded that of free doxorubicin. After conjugation the equilibrium binding constant of the DNA-drug complex (KA) decreased only by up to 3-fold. In 3-1 cells, but not in VI cells, DNA binding kinetics was an important factor and toxicity could be linearly correlated to 1/KA of conjugate (r=0.94). Drug accumulation decreased with an increase in dextran size but drug removal was decreased only in V1 cells. It appeared that drug uptake was also sensitive to dextran conjugation. In Vl cells drug removal was sensitive to the P-gp inhibitor verapamil or energy starvation. Ratios of V1/3-1 toxicity, drug accumulation and drug removal correlated linearly with log dextran size. When these ratios equaled 1, dextran sizes were estimated to be 32, 103 and 21 kDa, respectively.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1976

A comparison of the anaphylactoid actions of a synthetic linear dextran and a natural branched dextran.

Synthetic linear dextran of molecular weight 40,000 produces the systemic anaphylactoid reaction in rats although it is about 4 times less active than the natural branched dextran of similar molecular weight. Similarly, it is less active on local injection into the foot or skin. However, in rats which have been bred for non-reactivity to systemic dextran, it is more active on local injection, resembling the activity of a branched natural dextran of much lower molecular weight (6,000). In human skin, the synthetic linear 40,000 sample is also more active than the natural branched sample of similar molecular weight in producing a wheal and erythema. The results suggest that the dextran receptor in the skin of man may be similar to that in rats genetically resistant to systemic dextran.

Anaphylaxis↗

PubMed1980

A new immunochemical purity test for clinical dextran. Methodology and studies on clinical dextran preparations.

A simple immunochemical procedure, based on reversed single radial immunodiffusion (RSRI) was developed to detect commonly occurring traces of antigenic contaminants in clinical dextran. High-titred antisera against non-dextran components of Leuconostoc mesenteroides NRRL B512 were produced and served as analytical reagents. Dextran samples were incorporated into a gel layer. Presence of contaminants is revealed by precipitate formation following application of antiserum to a well cut into the gel. Antigenic contaminants can be detected in concentrations exceeding 10 ppm by the Leuconostoc-RSRI test. Screen results on 119 clinical dextran samples from manufactures in different countries disclosed presence of antigen traces in 82% of preparations. Introduction of the new test and improved purification measures at Pharmacia AB resulted in purer clinical dextran with negative RSRI test scores in 99% of batches produced. Only batches passing this test are released for clinical use. Although no direct correlation was found between contaminant levels and incidence of dextran reactions, antigenic contaminants may play a contributory role in elicitation of mild reactions.

Animals↗

PubMed1989

Thromboprophylaxis in hip arthroplasty. Dextran with graded compression or preoperative dextran compared in 150 patients.

Totally, 150 patients, subjected to total hip arthroplasty, were randomly allocated into three prophylactic groups with either conventional dextran alone or with additional graded compression stockings or with additional preoperative administration of dextran. The overall frequency of deep venous thrombosis (DVT), as studied by radioactive fibrinogen uptake test and ascending phlebography of the operated on thigh was in the conventional dextran group 46 percent, the additional stockinged group 30 percent, and in the additional preoperative dextran group 52 percent. In the stockinged group, there was a lower frequency of DVT in the nonoperated on leg as well as, on an average, about 350 mL less peroperative bleeding as compared with the other two groups. No adverse reaction occurred from dextran administration. Increased and prolonged postoperative administration of dextran decrease the number of femoral DVTs.

Aged↗

PubMed1992

[Randomized double-blind study of therapy of sudden deafness. Low molecular weight dextran + naftidrofuryl vs. low molecular weight dextran + placebo].

Eighty patients with idiopathic sudden deafness existing no longer than 10 days were included in a prospective randomized double-blind study. Patients were treated for 10 days with infusions of either 10% low-molecular weight dextran or the combination of low-molecular weight dextran with naftidrofuryl. Before treatment and after 10 days hearing loss in the affected ear was determined at 0.5, 1, 2, 3, 4 and 6 kHz. The mean hearing loss was then calculated as the average from these values. During monotherapy with low-molecular weight dextran the mean hearing loss decreased from 40 to 27 dB compared to 38 to 17 dB when naftidrofuryl treatment was added (p < 0.01 between groups). A significant benefit of naftidrofuryl on hearing loss was also found at frequencies between 0.5 and 3 kHz. Furthermore, patients reported better improvement of tinnitus when naftidrofuryl was combined with dextran. Two patients receiving dextran alone developed side effects: one had an allergic reaction causing withdrawal of treatment, which the other case had vertigo, nausea and headache with spontaneous recovery. The results of the study showed that treatment with naftidrofuryl in addition to hemodilution with low-molecular weight dextran was of therapeutic benefit in the therapy of sudden deafness without increasing the rate of side effects.

Administration, Oral↗

PubMed1989

Preliminary studies on the in vivo fate of FITC-dextrans and naproxen-dextran ester prodrugs administered i.v. to rabbits.

The plasma half life and the urinary recovery after i.v. administration to rabbits (35 mg/kg) of FITC-dextrans and naproxen-dextran ester prodrugs of molecular weights 40,000 and 70,000 were determined by employing a HP(SEC) procedure with fluorescence detection. The conjugates disappeared from the blood stream roughly according to first-order kinetics at a rate only slightly influenced by the molecular weight and faster than the parent carrier dextrans. 15-30% of the dose of the derivatives was eliminated through the kidneys as compared to 44% (T-40) and 17% (T-70) of the parent dextrans. Liver uptake of the compounds was assumed to be the main additional elimination pathway as 46% of an i.v. dose of FITC dextran T-70 was found in the liver four hours after the injection, whereas only minor amounts were detected in the spleen, lungs and the kidneys. The molecular weight distribution of the conjugates in the circulation shifted continuously in the high molecular weight direction. The role of the liver in plasma clearance of the conjugates and the influence of the molecular weight and electric charge on the in vivo fate of the dextran derivatives are discussed.

Animals↗

PubMed2000

Structure of dextran-magnetite complex: relation between conformation of dextran chains covering core and its molecular weight.

A homologous series of dextran-magnetite complex (DM) was synthesized using alkali-treated dextrans with various molecular weights from 1800 to 27000. The structure of DM particles in water, particularly effect on molecular weight of dextran, was studied. The number of dextran chains binding to a core is possibly determined by the steric hindrance between dextran chains covering core. The conformation of dextran chains may change from a fully extended state to a random-coiled state with an increase in molecular weight.

Journal Article↗

PubMed1975

Heparin, dextran 1000 and metastasis formation after I.V. tumour cell injection in dextran non-sensitive rats.

The present study of the effect of heparin and dextran 1000 on the metastasis formation after i.v. tumour cell injection in dextran non-sensitive rats using a syngeneic 20-methylcholanthrene induced fibrosarcoma showed that heparin treatment decreased with formation of pulmonary metastases in animals both untreated and treated with dextran 1000. Treatment with dextran 1000 increased the formation of pulmonary metastases in animals both untreated and treated with heparin and the effect of dextran 1000 was thus not affected by heparin treatment. Heparin did not have any direct action on the tumour cells, which influenced metastasis formation. The data suggest that heparin acts as an anticoagulant with decreased microthrombus formation around lodged cells and that dextrax 1000 stimulates metastasis formation primarily by mechanisms other than intravascular coagulation.

Animals↗

PubMed2002

Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA-dextran conjugate.

We have studied the cytostatic effects of sodium phenylacetate (NaPA) in association with several substituted dextrans on human tumor melanoma 1205LU cells. We show that NaPA alone inhibits the growth of these cells (IC50 = 3.9 mM) while a weak inhibitory effect appears at a concentration of 37 microM (10 microg/ml) for a dextran methyl carboxylate benzylamide (LS17-DMCB). The precursors of LS17-DMCB [T40 Dextran and carboxymethyl dextran (LS17-DMC)] did not affect the growth of 1205LU cells. To potentiate the inhibitory activity of NaPA at low concentrations (below 5.6 mM), we have tested NaPA and LS17-DMCB in physical mixture (association) or linked together covalently (this conjugate is termed 'LS17-NaPaC'). We have observed an increase of the 1205LU cell growth inhibition effect with NaPA in association (IC50 1.8 mM). For a concentration of 5 mM of NaPA (free in the case of association or linked in the case of conjugate), the association with dextran derivative exhibits a 4.6-fold higher efficacy than with NaPA alone (9 versus 41% surviving fraction), while the conjugate is 1.3-fold smaller (52% growth inhibition). By performing isobologram analysis of the IC50 data, we have shown a synergistic effect for a particular molar ratio of NaPA and LS17-DMCB (NaPA:LS17-DMCB = 0.35).

Animals↗