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At least 199 records · Page 11Linked to original sources
PubMed1994

DNA sequence affects nucleosome ordering on replicating plasmids in transfected COS-1 cells and in vitro.

Nucleosome ordering on a variety of replicating plasmids, assembled into chromatin in transfected COS-1 cells, was studied by micrococcal nuclease digestion of isolated nuclei. Generally, no more than three well defined multiples of a unit nucleosome repeat, which resembled the first three bands of the (187 +/- 5 base pair (bp)) cellular chromatin ladder, could be detected in constructs that contained a near-minimal SV40 replication origin. In contrast, constructs that additionally contained the SV40 early region exhibited significantly more regular nucleosome arrangements. In some cases, eight to nine multiples of a 203 +/- 5-bp repeat could be resolved. The presence of the SV40 early region was necessary for physiological nucleosome alignment over the SV40 late and ori regions, or onto adjacent pBR327 DNA. In an in vitro chromatin assembly system, using purified chicken erythrocyte histones plus polyglutamic acid, a portion of SV40 DNA became packaged into a highly ordered 200 +/- 5-bp nucleosome array, which encompassed the early region and extended for about 2800 bp. The data suggest that in the cell nucleus, nucleosome ordering on SV40 DNA might spread from sequences in the early region, close to where transcription terminates, probably as a consequence of histone H1-nucleosome interactions.

Animals↗
PubMed1993

High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors.

Scavenger receptors interact with a variety of modified proteins, mediate their endocytosis and degradation, and may play an important role in protein catabolism and pathogenic processes such as atherosclerosis, aging, and diabetes. Many scavenger receptors have been detected kinetically but few such binding proteins have actually been identified. Recently, we found that two membrane-associated proteins, gp30 and gp18, interact more avidly with albumins conformationally modified by chemical means or by surface adsorption to colloidal gold particles than with native albumin. In this study, we show that gp30 and gp18 behave similarly to other known scavenger receptors. Competition studies indicate a similar ligand binding profile to other known scavenger receptors. Polyanionic molecules (dextran sulfate, fucoidan, polyglutamic acid, polyinosinic acid, heparin) and modified albumins such as formaldehyde-treated or maleylated albumin (Mal-bovine serum albumin) competed with albumin conjugated to colloidal gold particles (A-Au) for the blotting of gp30 and gp18. A-Au and Mal-bovine serum albumin bound cultured endothelial cells with high affinity. Modified and native albumins were each internalized, but only modified albumins were then released degraded. Inhibition studies revealed that only the same molecules that were effective in blocking A-Au blotting of gp30 and gp18, also inhibited A-Au degradation. Addition of the lysosomotropic agent chloroquine resulted in more than 70% inhibition of degradation. Differential processing of A-Au by cultured smooth muscle and endothelial cells along with fibroblasts was observed in a manner consistent with gp30 and gp18 expression. Cumulatively, these results suggest that gp30 and gp18 may mediate the high affinity binding, endocytosis, and degradation of conformationally modified albumins but not native albumin.

Albumins↗
PubMed1996

[Preparation and in vitro activity of monoclonal antibody-pharmorubicin immunoconjugates].

Bifunctional agent adipic dihydrate was used to form hydrazon bond between polyglutamic acid (PGA) and pharmorubicin (PAR). Under controlled condition, a relatively high rate of conjugation was obtained with no self-condensation. The value of PGA/PAR was in positive portion with the molecular weight (MW) of PGA: per 8-11 glutamic acid monomer linking one pharmorubicin. When PGA of MW 14,300 was used as carrier, the ratio of PGA/PAR was 1:11. After conjugating with anti-hepatoma monoclonal antiboty (McAb), an immunoconjugate of McAb:PGA:PAR being 1:2:22 was obtained. The immunoconjugate retained the binding activity to targeted cell compared with the purified and the oxidized antibody. Pharmacological studies in vitro showed lower cytotoxicity of the immunoconjugate than the free drug, but selective cytotoxicity directed by antibody was observed. Consequently, the immunoconjugate McAb-PGA-PAR with high ratio of drug/McAb as well as moderate targeting cytotoxity in vitro was successfully prepared. That makes it possible for the preparation of cell-targeted drug which is expected to be benificial to tumor treatment.

Antibodies, Monoclonal↗
PubMed2005

Prevention of postoperative peritoneal adhesions: effects of lysozyme, polylysine and polyglutamate versus hyaluronic acid.

OBJECTIVE: Intraperitoneal adhesions are an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. In the present study we hypothesized that a combination of polypeptides with different surface properties, resulting in fine disperse low-soluble complexes, could be of benefit in the prevention of abdominal adhesions. MATERIAL AND METHODS: Various polypeptides including lysozyme, polyglutamate, polylysine and combinations of all three were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The extent of peritoneal adhesions to the injured area was measured and expressed as a percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and the Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function caused by the chemicals. RESULTS: Significant differences were seen among the treatment groups (p<0.001). Both polyglutamate and lysozyme, and polyglutamate together with polylysine significantly decreased adhesion formation as compared to hyaluronic acid. The polylysine-polyglutamate combination was still visible macroscopically on the peritoneal surface after 1 week, though not after 1 month. The polyglutamate-lysozyme mixture was less effective than these individual components alone. The chemicals did not show any toxic effects or altered function in macrophage cell culture. CONCLUSIONS: Lysozyme, polyglutamate and, most effectively, a polyglutamate-polylysine combination significantly decreased experimental abdominal adhesion formation. A strong mechanical connection to the wound and prolonged attendance in the surface were noted. Peritoneal phagocyte function did not seem to be influenced by the chemicals.

Adjuvants, Immunologic↗
PubMed1983

Molecular basis for the interaction of polyglutamates of folic acid and its analogs with dihydrofolate reductase.

Fluorimetric titration has been used to measure the dissociation constants for the complexes of folate, pteroyltriglutamate and pteroylheptaglutamate with dihydrofolate reductase purified from Lactobacillus casei, Streptococcus faecium (isoenzyme 2) and bovine liver. Effects of pH, temperature, salt concentration and second ligands have been examined. The method is shown to be unsuitable for methotrexate complexes. The polyglutamates do not bind more tightly than folate to the S. faecium reductase under any conditions examined, but bind somewhat more tightly than folate to the L. casei reductase at low pH (less than 7) and to the bovine liver enzyme at pH 7-9. Increasing concentrations of KC1 decrease the binding of all three ligands to the L. casei and bovine liver enzymes. Increasing pH markedly raises the dissociation constants for all complexes of the L. casei reductase, but has only slight effects on the complexes of the S. faecium reductase. Complexes of the bovine enzyme are affected to an intermediate degree by pH, but the folate complex is affected much more than those of the polyglutamates. Model building studies have been performed with a three-dimensional model of the complex of L. casei reductase with NADPH and methotrexate. Additional glutamyl groups were added in gamma-linkage to the glutamate moiety of the complexed methotrexate. A proposed mode of binding of the pteroyl polyglutamates is discussed and sequence comparisons are used to predict residues that might be involved in polyglutamate binding by reductase from other sources.

Animals↗
PubMed1991

Hepatic methotrexate content and progression of hepatic fibrosis: preliminary findings.

Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver.

Adult↗
PubMed1983

Effects of folinic acid on hepatoma cells containing methotrexate polyglutamates.

The effects of folinic acid on a toxic pulse exposure of cultured hepatoma cells to methotrexate (4-amino-10-methylpteroylglutamic acid) is reported. Inclusion of folinic acid (5-formyl-5,6,7,8-tetrahydropteroylglutamic acid) (10 micro M) with the 2-hr pulse of methotrexate (10 micro M) nearly completely prevents the uptake and gamma-glutamylation of methotrexate and prevents toxicity. Addition of folinic acid after methotrexate results in a partial rescue that is time and concentration dependent. Restoration of cell growth in the presence of increasing amounts of folinic acid is accompanied by a concentration-dependent elevation in tritium release from [5-3H]deoxyuridine. In the absence of folinic acid, the release of tritium from [5-3H]deoxyuridine remains inhibited for three days after exposure to methotrexate, which can be related to the cellular formation and retention of methotrexate polyglutamates. Following the 2-hr pulse of methotrexate, the cellular pool consists of 70% polyglutamates of which the predominant species has three glutamate residues (4-NH2-10-CH3PteGlu3). When methotrexate is removed from medium, following the pulse, unmetabolized methotrexate rapidly leaves the cells, and 4-NH2-10-CH3PteGlu3 is converted to methotrexate polyglutamates containing four to six glutamate residues. Addition of folinic acid after the methotrexate pulse prevents the conversion of 4-NH2-10-CH3PteGlu3 to the higher-chain-length derivatives and causes a reduction in the total methotrexate cell pools over the next 48 hr. These results suggest that the effects of folinic acid on methotrexate polyglutamates may play a role in the rescue of cells containing these derivatives.

Animals↗
PubMed2000

Influence of alkali cation nature on structural transitions and reactions of biopolyelectrolytes.

A general thermodynamic analysis is presented, describing how counterion species of different nature, but the same valency, influence polyelectrolyte transformations and reactions of the general form: PA1.B1-M(+)-->PA2.B2M+ + (B1 - B2)M+. Here PA1 and PA2 are two different states or structural forms of a polyanion, B1 and B2 are the number of M+ ions thermodynamically bound to the polyanions PA1 and PA2, respectively. The specific effects of the two counterions, M1+ and M2+, on this equilibrium can be simply related to the quotient of their selectivity constants, D2M2M1/D1M2M1, for the polyion states 1 and 2. We analyze how different monovalent counterions (particularly, sodium and potassium) affect polyelectrolyte reactions and transformations such as, e.g., the DNA helix-coil transition. Previous experimental results on the competition between DNA and the synthetic polyanion, poly(methacrylic acid), for binding to the synthetic polycation, poly(N-ethylvinylpyridinium), has been investigated with respect to sodium and potassium ion specificity, using our model. We also discuss the DNA-histone disassembly/assembly reaction modeled as a competition of two polyanions for binding to a polycation.

Acrylates↗