UMLS:C0393754 - FACTA Search

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Query: UMLS:C0393754 (HSA)
2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neutron capture reaction 10B(1n,4He)7Li produces two energetic particles, 4He2+ and 7Li3+ that are strongly cell toxic. Due to the short range of these nuclear fragments (5-9 microns) mainly those cells that have bound or internalized a 10B-containing substance are growth-inactivated. The most critical and difficult step in an efficient boron neutron capture therapy (BNCT) is the tumour targeting. It is today possible to synthesize a large number of boron compounds and conjugate them to tumour-seeking macromolecules, such as monoclonal antibodies or different polypeptides. The boron-containing substances presently considered for therapy are sulfhydryl boron hydride (BSH) and boron-phenylalanine, (BPA) for the treatment of gliomas and malignant melanomas respectively. Other boronated compounds considered are ligands for receptor-amplified tumour cells, antibodies for tumour cells with specific antigens and thioureas for treatment of melanotic melanomas. The required boron concentration is given by the relative dose due to neutron capture in 10B and that of the competing capture reactions in nitrogen and hydrogen. Capture in nitrogen produces protons with a range of about 10-11 microns and this gives a radiation dose to all cells in the neutron activated area. Calculations show that the local concentration of 10B near the critical radiation target, DNA, must be higher than 10 ppm (10 micrograms/g). Increased emphasis will be put on the development of combinations of treatments that fulfil the requirements for attacking the microscopic spread of the tumour.
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PMID:Present status of boron neutron capture therapy. 129 Jun 30

Human macrophage colony-stimulating factor (hM-CSF) is a potent stimulator of the effector functions of monocytes/macrophages. We investigated the antitumor effects of this factor in CDF1 male mice inoculated with L1210 cells, a mouse B-cell leukemia line. Mice preinoculated with various numbers of L1210 cells on day 0 were given intravenous injections of vehicle (human serum albumin; HSA) (100 micrograms/kg/day) or hM-CSF (20 micrograms/kg/day) for 3 days from day 1. In mice preinoculated with 10(2) L1210 cells but not with 10(3) or more L1210 cells, a marked increment in survival rate was observed with hM-CSF treatment. We next examined the effect of hM-CSF treatment combined with chemotherapy on the survival of mice that had been preinoculated with 10(5) L1210 cells. In our system, the administration of 4.9 mg/kg adriamycin (ADM) alone slightly prolonged survival of the tumor-bearing mice, but all of the mice died within 20 days. When hM-CSF was injected for 3 days before this ADM treatment, the invasion and proliferation of tumor cells in the liver and spleen were markedly inhibited and 50% of the mice were still alive at day 50. We detected inhibitory activity toward L1210 growth in serum of mice administered with hM-CSF, and the degree of the inhibitory activity was correlated with the level of nitrite (NO2-) in the serum. When L1210 cells were co-cultured with peritoneal macrophages from mice intraperitoneally injected with hM-CSF, the uptake of [3H]thymidine in L1210 cells was inhibited. The inhibition was abolished by the addition of NG-monomethyl-L-arginine, an inhibitor of NO2- synthesis, suggesting that the reactive nitrogen oxide intermediate is involved in hM-CSF-induced inhibition of L1210 growth.
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PMID:Augmentation of cancer chemotherapy by preinjection of human macrophage colony-stimulating factor in L1210 leukemic cell-inoculated mice. 753 4

This study evaluated the effects of pentoxifylline (PTX) on post-thaw semen parameters as well as the hypoosmotic swelling (HOS) test. Fourteen samples were evaluated for volume, count, motility, % grade A sperm, and HOS test. Two aliquots were frozen, one in freezing medium and the other in a 3 mM solution of PTX and freezing medium. Both groups were frozen in liquid nitrogen vapors for 30 min. Thawing was performed at 37 degrees C for 15 min, followed by a wash with 2 parts 0.5% HSA/MHTF to 1 part sample. Pellets were resuspended in 0. MHTF and then evaluated as described above. In addition, motility was evaluated 2 h post-thaw. Following freeze-thaw, the mean motile densities were similar (17.5 x 10 motile/mL vs. 20.4 x 10(6) motile/mL for PTX and control, respectively). Two hours post-thaw, the PTX group had a mean sperm motility of 31.3% vs. 37.7% for the control group (p > .05). There were no significant differences in % grade A sperm in PTX (13.0%) vs. control (12.0%). Similarly, HOS scores did not improve following cryopreservation (43.0% and 50.6% for PTX and control, respectively). Thus, no improvement was found by freezing sperm with PTX.
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PMID:Effect of pentoxifylline added to freezing media on subsequent post-thaw hypoosmotic swelling test and other semen parameters. 858 71

Large animal studies have been utilized to define tolerance of normal brain to irradiation and verify treatment planning programs with two recently installed epithermal neutron beams. The normal brain tolerance studies utilized two biological endpoints, magnetic resonance visible damage only and neurologic signs progressing to death. The studies focused on defining the proton RBE for the contaminant fast neutrons, and from nitrogen capture of thermal neutrons and boron capture reaction biologic effect. The proton RBE was approximately 3.0 to 6.7, depending on whether a dose reduction factor for the low gamma dose rate was employed. The microscopic distribution of the boron compounds, coupled with the extremely short length of the fission fragments from thermal neutron capture by 10B yields an observed biologic effect much less than would be expected from such high LET irradiation. This observed biologic effect, which is a product of the microdistribution of the boron atom and the relative biologic effect of the fission fragments has been termed compound factor. The compound factor was based on the calculated physical dose from the fission fragment in blood based on measured blood 10B concentration. The approximate compound factor for BSH was studied at the two institutions and it ranged from 0.27 to 0.55, depending on the site and the endpoint chosen. The mean compound factor for BPA was only studied at one site and was found to be 1.1 for both endpoints. The increase in the compound factor for BPA is in keeping with previous calculations based on the differences in compound distribution. Results of these studies has helped the initiation of phase I and phase II clinical trials at Brook haven National Laboratory and the planned European clinical trials at Petten, The Netherlands.
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PMID:A review: CNS effects and normal tissue tolerance in dogs. 915 Dec 25

Autologous BM and PB HPC are usually stored from weeks to months until reinfusion after myeloablative chemotherapy. HPC have been stored for up to 16 months at -90 degrees C, using a mixture of 5% DMSO, 6% hydroxyethyl starch (HES), and 4% HSA as a cryoprotectant. Long-term storage (LTS) has usually entailed rate-controlled freezing using 10% DMSO and preservation in liquid nitrogen. The effects of LTS at -90 degrees C on the in vitro cell recovery, viability, and colony-forming unit-granulocyte macrophage (CFU-GM) clonogenic potential of autologous HPC that were not transplanted was studied. Sixteen BM and sixteen PB HPC had been cryopreserved for a median of 53 months (range 27-71) and 35 months (range 26-78), respectively. Samples of frozen HPC were thawed after 48 h, and the nucleated cell count, viability by trypan blue exclusion, and culture for CFU-GM were obtained. Following LTS, the cells were thawed and examined using the same assays. No difference in the median percentage recovery of nucleated cells was found in either the BM or PB HPC between the samples stored for 48 h and after LTS (5.73 x 10(9) versus 5.61 x 10(9) and 6.20 x 10(9) versus 5.78 x 10(9), respectively). In addition, no difference in median percentage viability was found in either the BM or PB HPC sampled at 48 h and at the end of LTS (75% versus 74% and 75% versus 76%, respectively). Finally, the median number of CFU-GM cultured from BM HPC at 48 h was 2.41 x 10(5) (range 0.33-11.01 x 10(5)) and at the end of LTS was 1.93 x 10(5) (range 0.32-10.55), representing a median recovery of 93% (range 19%-308%). Similarly, the median number of CFU-GM cultured from PB HPC was 1.66 x 10(5) (range 0-50.57) and at the end of LTS was 0.93 x 10(5) (range 0-44.9), representing a median recovery of 80% (range 36%-165%). This difference in percentage recovery was not significant (p = 0.514). There was poor correlation between the number of nucleated cells harvested and the percentage recovery of nucleated cells, cell viability, or CFU-GM for either the BM or PB HPC. Similarly, there was poor correlation between the number of CFU-GM in the harvest and their percentage recovery following LTS for both BM and PB HPC. Finally, there was poor correlation between the storage time of the BM or PB HPC and the percentage recovery of nucleated cells, cell viability, and CFU-GM. These data suggest that LTS of HPC at -90 degrees C is not associated with decreased recovery of nucleated cells or in vitro viability and is associated with only a modest decrease in clonogenic potential. This indicates that storage of HPC at -90 degrees C for periods in excess of 3 years is possible.
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PMID:Effects of long-term storage at -90 degrees C of bone marrow and PBPC on cell recovery, viability, and clonogenic potential. 973 70

Three novel phosphorus-containing analogues of H(5)DTPA (DTPA = diethylenetriaminepentaacetate) were synthesised (H6L1, H5L2, H5L3). These compounds have a -CH2-P(O)(OH)-R function (R = OH, Ph, CH2NBn2) attached to the central nitrogen atom of the diethylenetriamine backbone. An NMR study reveals that these ligands bind to lanthanide(III) ions in an octadentate fashion through the three nitrogen atoms, a P-O oxygen atom and four carboxylate oxygen atoms. The complexed ligand occurs in several enantiomeric forms due to the chirality of the central nitrogen atom and the phosphorus atom upon coordination. All lanthanide complexes studied have one coordinated water molecule. The residence times (tau(M)298) of the coordinated water molecules in the gadolinium(III) complexes of H6L1 and H5L2 are 88 and 92 ns, respectively, which are close to the optimum. This is particularly important upon covalent and noncovalent attachment of these Gd(3+) chelates to polymers. The relaxivity of the complexes studied is further enhanced by the presence of at least two water molecules in the second coordination sphere of the Gd(3+) ion, which are probably bound to the phosphonate/phosphinate moiety by hydrogen bonds. The complex [Gd(L3)(H2O)](2-) shows strong binding ability to HSA, and the adduct has a relaxivity comparable to MS-325 (40 s(-1) mM(-1) at 40 MHz, 37 degrees C) even though it has a less favourable tau(M) value (685 ns). Transmetallation experiments with Zn(2+) indicate that the complexes have a kinetic stability that is comparable to-or better than-those of [Gd(dtpa)(H2O)](2-) and [Gd(dtpa-bma)(H2O)].
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PMID:Lanthanide(III) complexes of novel mixed carboxylic-phosphorus acid derivatives of diethylenetriamine: a step towards more efficient MRI contrast agents. 1467 62

The methylotrophic yeast, Pichia pastoris, is widely used as a host strain for the production of a variety of heterologous proteins. We used P. pastoris for the production of recombinant human serum albumin (rHSA). In several runs of fed-batch fermentation, rapid degradation of rHSA was observed, coinciding with a sudden increase of protease activity in the culture broth. Monitoring the changes in the concentration of the medium components during fermentation suggested that this phenomenon was caused by nitrogen starvation. Increased initial concentrations of ammonia and phosphoric acid in the medium prevented the protease production during fermentation. Using this improved medium, stable production of rHSA of around 1.4 g/l was achieved. Although protease activity in the culture broth of the improved medium was not detected by the casein plate method at the end of fermentation, potential protease activity remained and could be activated by decreasing the pH of the culture broth, a high degradation rate of 660 mg HSA/l/h was observed at pH 4.3, but degradation did not occur above pH 5.9.
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PMID:High-level expression of recombinant human serum albumin from the methylotrophic yeast Pichia pastoris with minimal protease production and activation. 1623 98

With the objective of tuning the lipophilicity of ligands and maintaining the neutrality and stability of Gd(III) chelate, we designed and synthesized two bis(amide) derivatives of TTDA, TTDA-BMA and TTDA-BBA, and a mono(amide) derivative, TTDA-N-MOBA. The ligand protonation constants and complex stability constants for various metal ions were determined in this study. The identification of the microscopic sites of protonation of the amide ligand by 1H NMR titrations show that the first protonation site occurs on the central nitrogen atom. The values of the stability constant of TTDA-mono and bis(amide) complex are significantly lower than those of TTDA and DTPA, but the selectivity constants of these ligands for Gd(III) over Zn(II) and Cu(II) are slightly higher than those of TTDA and DTPA. On the basis of the water-exchange rate values available for [Gd(TTDA-BMA)(H2O)], [Gd(TTDA-BBA)(H2O)] and [Gd(TTDA-N-MOBA)(H2O)]-, we can state that, in general, the replacement of one carboxylate group by an amide group decreases the water-exchange rate of the gadolinium(III) complexes by a factor of about three to five. The decrease in the exchange rate is explained in terms of a decreased steric crowding and charge effect around the metal ion when carboxylates are replaced by an amide group. In addition, to support the HSA protein binding studies of lipophilic [Gd(TTDA-N-MOBA)(H2O)]- and [Gd(TTDA-BBA)(H2O)] complexes, further protein-complex binding was studied by ultrafiltration and relaxivity studies. The binding constants (KA) of [Gd(TTDA-N-MOBA)(H2O)]- and [Gd(TTDA-BBA)(H2O)] are 8.6 x 10(2) and 1.0 x 10(4) dm3 mol(-1), respectively. The bound relaxivities (r1(b)) are 51.8 and 52 dm3 mmol(-1) s(-1), respectively. The KA value of [Gd(TTDA-BBA)(H2O)] is similar to that of MS-325 and indicates a stronger interaction of [Gd(TTDA-BBA)(H2O)] with HSA.
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PMID:Synthesis, complexation and water exchange properties of Gd(III)-TTDA-mono and bis(amide) derivatives and their binding affinity to human serum albumin. 1759 91

In recent studies, the cytotoxic activity of NO has been investigated for its potential use in anticancer therapies. Nitrosated human serum albumin (NO-HSA) may act as a reservoir of NO in vivo. However, there are no published reports regarding the effects of NO-HSA on cancer. Therefore, the present study investigated the antitumor activity of NO-HSA. NO-HSA was prepared by incubating HSA, which had been sulfhydrylated using iminothiolane, with isopentyl nitrite (6.64 mol NO/mol HSA). Antitumor activity was examined in vitro using murine colon 26 carcinoma (C26) cells and in vivo using C26 tumor-bearing mice. Exposure to NO-HSA increased the production of reactive oxygen species in C26 cells. Flow cytometric analysis using rhodamine 123 showed that NO-HSA caused mitochondrial depolarization. Activation of caspase-3 and DNA fragmentation were observed in C26 cells after incubation with 100 muM NO-HSA for 24 h, and NO-HSA inhibited the growth of C26 cells in a concentration-dependent manner. The growth of C26 tumors in mice was significantly inhibited by administration of NO-HSA compared with saline and HSA treatment. Immunohistochemical analysis of tumor tissues demonstrated an increase in terminal deoxynucleotidyl transferase dUTP nickend labeling-positive cells in NO-HSA-treated mice, suggesting that inhibition of tumor growth by NO-HSA was mediated through induction of apoptosis. Biochemical parameters (such as serum creatinine, blood urea nitrogen, aspartate aminotransferase, and alanine aminotransferase) showed no significant differences among the three treatment groups, indicating that NO-HSA did not cause hepatic or renal damage. These results suggest that NO-HSA has the potential for chemopreventive and/or chemotherapeutic activity with few side effects.
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PMID:Design and evaluation of S-nitrosylated human serum albumin as a novel anticancer drug. 1821 31

The (low loaded) biological nutrient removing activated sludge process is the generally accepted and applied municipal wastewater treatment method in the Netherlands. The hydraulical and biological flexibility, robustness and cost efficiency of the process for advanced removal of nutrients like nitrogen and phosphorus without (too much) chemicals results in a wide application of the activated sludge process within Dutch waterboards. Presumably, wastewater treatment plants will have to contribute to the improvement of the quality of the receiving surface waters by producing cleaner effluent. In this perspective, the Dutch research organisation STOWA initiated a research project entitled "The Boundaries of the Activated Sludge Process" to investigate the possibilities and limitations of activated sludge processes to improve the effluent quality. It is concluded that the activated sludge process as applied and operated at WWTP's in the Netherlands has the potential to perform even better than the current effluent discharge standards (10 mg Ntotal/l and 1 mg Ptotal/l). Reaching the B-quality effluent (<5mg Ntotal/l and <0.3 mg Ptotal/l) will be possible at almost all WWTPs without major adjustments under the conditions that: the sludge load is below 0.06 kg BOD/kg TSS.d the internal recirculation is above 20 the BOD/N ratio of the influent is above 3. Complying with the A-quality effluent (<2.2 Ntotal/l and <0.15 mg Ptotal/l) seems to be difficult (but not impossible) and requires more attention and insight into the activated sludge process. Optimisation measures to reach the A-quality effluent are more thorough and are mostly only achievable by additional construction works (addition of activated sludge volume, increasing recirculation capacity, etc.). It is furthermore concluded that the static HSA-results are comparable to the dynamic ASM-results. So, for fast determinations of the limits of technology of different activated sludge processes static modelling seems to by sufficient.
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PMID:The limits and ultimate possibilities of technology of the activated sludge process. 1900 24

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