共查询到20条相似文献,搜索用时 15 毫秒
1.
Yang-Yang Chen Lin Xiao Jun-Hui Cui Gui-Fang Chen Juan Zhang Ping Wang 《Food biophysics》2013,8(4):282-289
In view of synergistic effect of resveratrol and insulin in the prevention and treatment of many chronic diseases, the interaction between them was studied and its biological implication was further discussed. Insulin could interact with resveratrol to form 1:1 complex with the binding constant of 1.03?×?103 M?1 at 298 K. The binding was spontaneous and insulin/resveratrol complex formation was an exothermal reaction. Hydrogen bond and van der Waals force played key roles in the binding process. Kinetic study indicates that resveratrol binding to insulin conformed to the first-order exponential decay function. The interaction decreased the polarity around tyrosine residue and α-helical content, destroyed the disulfide bridges, depolymerized insulin dimers to monomer, and altered the orientation of aromatic side chains in the insulin. Additionally, insulin increased resveratrol stability. These results well confirm synergistic effect of resveratrol and insulin in vitro. It would give a deeper insight into resveratrol as a kind of food functional factor. 相似文献
2.
The activity of alanine aminotransferase (ALT; E.C. 2.6.1.2) is often changed upon inflammatory responses in animals. Rare
earths was shown to provoke various inflammatory responses both in rats and mice; however, the molecular mechanism by which
rare earths exert its toxicity has not been completely understood, especially, we know little about the mechanism of the interaction
between CeCl3 and ALT. In this report, we investigated the mechanisms of CeCl3 on ALT activity in vivo and in vitro. Our results showed that Ce3+ could significantly activate ALT in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.018 μM and 1,380 unit mg−1 protein min−1, respectively, at a low concentration of Ce3+, and 0.027 μM and 624 unit mg−1 protein min−1, respectively, at a high concentration of Ce3+. By UV absorption and fluorescence spectroscopy assays, the Ce3+ was determined to be directly bound to ALT; the binding site of Ce3+ to ALT was 1.72, and the binding constants of the binding site were 4.82 × 108 and 9.05 × 107 L mol−1. Based on the analysis of the circular dichroism spectra, it was concluded that the binding of Ce3+ altered the secondary structure of ALT, suggesting that the observed enhancement of ALT activity was caused by a subtle structural
change in the active site through the formation of the complex with Ce3+. 相似文献
3.
James C. Fredenburgh Beverly A. Leslie Alan R. Stafford Teresa Lim Howard H. Chan Jeffrey I. Weitz 《The Journal of biological chemistry》2013,288(41):29394-29402
The nonspecific binding of heparin to plasma proteins compromises its anticoagulant activity by reducing the amount of heparin available to bind antithrombin. In addition, interaction of heparin with fibrin promotes formation of a ternary heparin-thrombin-fibrin complex that protects fibrin-bound thrombin from inhibition by the heparin-antithrombin complex. Previous studies have shown that heparin binds the E domain of fibrinogen. The current investigation examines the role of Zn2+ in this interaction because Zn2+ is released locally by platelets and both heparin and fibrinogen bind the cation, resulting in greater protection from inhibition by antithrombin. Zn2+ promotes heparin binding to fibrinogen, as determined by chromatography, fluorescence, and surface plasmon resonance. Compared with intact fibrinogen, there is reduced heparin binding to fragment X, a clottable plasmin degradation product of fibrinogen. A monoclonal antibody directed against a portion of the fibrinogen αC domain removed by plasmin attenuates binding of heparin to fibrinogen and a peptide analog of this region binds heparin in a Zn2+-dependent fashion. These results indicate that the αC domain of fibrinogen harbors a Zn2+-dependent heparin binding site. As a consequence, heparin-catalyzed inhibition of factor Xa by antithrombin is compromised by fibrinogen to a greater extent when Zn2+ is present. These results reveal the mechanism by which Zn2+ augments the capacity of fibrinogen to impair the anticoagulant activity of heparin. 相似文献
4.
Yanmei Duan Na Li Chao Liu Huiting Liu Yaling Cui Han Wang Fashui Hong 《Biological trace element research》2010,136(3):302-313
In order to study the mechanisms underlying the effects of TiO2 nanoparticles on lactate dehydrogenase (LDH, EC1.1.1.27), Institute of Cancer Research region mice were injected with nanoparticulate
anatase TiO2 (5 nm) of various doses into the abdominal cavity daily for 14 days. We then examined LDH activity in vivo and in vitro and
direct evident for interaction between nanoparticulate anatase TiO2 and LDH using spectral methods. The results showed that nanoparticulate anatase TiO2 could significantly activate LDH in vivo and in vitro; the kinetics constant (Km) and Vmax were 0.006 μM and 1,149 unit mg−1 protein min−1, respectively, at a low concentration of nanoparticulate anatase TiO2, and 3.45 and 0.031 μM and 221 unit mg−1 protein min−1, respectively, at a high concentration of nanoparticulate anatase TiO2. By fluorescence spectral assays, the nanoparticulate anatase TiO2 was determined to be directly bound to LDH, and the binding constants of the binding site were 1.77 × 108 L mol−1 and 2.15 × 107 L mol−1, respectively, and the binding distance between nanoparticulate anatase TiO2 and the Trp residue of LDH was 4.18 nm, and nanoparticulate anatase TiO2 induced the protein unfolding. It was concluded that the binding of nanoparticulate anatase TiO2 altered LDH structure and function. 相似文献
5.
Due to their unique fluorescent properties, quantum dots present a great potential for biolabelling applications; however,
the toxic interactions of quantum dots with biopolymers are little known. The toxic interactions of glutathione-capped CdTe
quantum dots with trypsin were studied in this paper using synchronous fluorescence spectroscopy, fluorescence emission spectra,
and UV–vis absorption spectra. The interaction between CdTe quantum dots and trypsin resulted in structure changes of trypsin
and inhibited trypsin's activity. Fluorescence emission spectra revealed that the quenching mechanism of trypsin by CdTe quantum
dots was a static quenching process. The binding constant and the number of binding sites at 288 and 298 K were calculated
to be 1.98 × 106 L mol−1 and 1.37, and 6.43 × 104 L mol−1 and 1.09, respectively. Hydrogen bonds and van der Waals' forces played major roles in this process. 相似文献
6.
Streptomyces lividans 1326 carries inducible mercury resistance genes on the chromosome, which are arranged in two divergently transcribed operons.
Expression of the genes is negatively regulated by the repressor MerR, which binds in the intercistronic region between the
two operons. The merR gene was expressed in E. coli using a T7 RNA polymerase/promoter expression system, and MerR was purified to around 95% homogeneity by ammonium sulfate
precipitation, gel filtration and affinity chromatography. Gel filtration showed that the native MerR is a dimer with a molecular
mass of 31 kDa. Two DNA binding sites were identified in the intercistronic mer promoter region by footprinting experiments. No evidence for cooperativity in the binding of MerR to the adjacent operator
sequences was observed in gel mobility shift assays. The dissociation constants (KD) for binding of MerR were: binding site I, 8.5 × 10−9 M; binding site II, 1.2 × 10−8 M; and for the complete promoter/operator region 1 × 10−8 M. The half-life of the MerR-DNA complex was 19.4 min and 18.8 min for binding site I and binding site II, respectively.
The KD value for binding of mercury(II)chloride to MerR, again determined by mobility shift assay, was 1.1 × 10−7 M.
Received: 18 August 1998 / Accepted: 5 May 1999 相似文献
7.
Liang C Xiao W Hao H Xiaoqing L Chao L Lei Z Fashui H 《Biological trace element research》2008,121(3):249-257
Mg2+ in various concentrations was added to purified Rubisco in vitro to gain insight into the mechanism of molecular interactions
between Mg2+ and Rubisco. The enzyme activity assays showed that the reaction between Rubisco and Mg2+ was two order, which means that the enhancement of Rubisco activity was accelerated by low concentration of Mg2+ and slowed by high concentration of Mg2+. The kinetics constant (K
m) and V
max was 1.91 μM and 1.13 μmol CO2 mg−1 protein∙min−1, respectively, at a low concentration of Mg2+, and 3.45 μM and 0.32 μmol CO2∙mg−1 protein∙min−1, respectively, at a high concentration of Mg2+. By UV absorption and fluorescence spectroscopy assays, the Mg2+ was determined to be directly bound to Rubisco; the binding site of Mg2+ to Rubisco was 0.275, the binding constants (K
A) of the binding site were 6.33 × 104 and 5.5 × 104 l·mol−1. Based on the analysis of the circular dichroism (CD) spectra, it was concluded that the binding of Mg2+ did not alter the secondary structure of Rubisco, suggesting that the observed enhancement of Rubisco carboxylase activity
was caused by a subtle structural change in the active site through the formation of the complex with Mg2+. 相似文献
8.
Manuela Pantusa Luigi Sportelli Rosa Bartucci 《European biophysics journal : EBJ》2012,41(11):969-977
The interaction between the natural polyphenol resveratrol and human serum albumin (HSA), the most abundant transport protein in plasma, has been studied in the absence and in the presence of up to six molecules of stearic acids (SA) pre-complexed with the protein. The study has been carried out by using the intrinsic fluorescence of both HSA and resveratrol. Protein and polyphenol fluorescence data indicate that resveratrol binds to HSA with an association constant k a ?=?(1.10?±?0.14)?×?105?M?1 and (1.09?±?0.02)?×?105?M?1, respectively, whereas Job plot evidences the formation of an equimolar protein/drug complex. Low SA content associated with HSA does not affect significantly the structural conformation of the protein and its interaction with resveratrol, whereas high SA content induces conformational changes in the protein, and reduces resveratrol binding affinity. The photostability of resveratrol in the different samples changes in the order: buffer <?(high [SA]/HSA)?<?HSA?<?(low [SA]/HSA). The results on (SA/HSA)-resveratrol samples highlight the ability of the protein to bind hydrophobic and amphiphilic ligands and to protect from degradation an important antioxidant molecule under biologically relevant conditions. 相似文献
9.
The microsolvation of taurine (TA) with one, two or three water molecules was investigated by a density functional theory
(DFT) approach. Quantum theory of atoms in molecules (QTAIM) analyses were employed to elucidate the hydrogen bond (H-bond)
interaction characteristics in TA-(H2O)n (n = 1–3) complexes. The results showed that the intramolecular H-bond formed between the hydroxyl and the N atom of TA are
retained in most TA-(H2O)n (n = 1–3) complexes, and are strengthened via cooperative effects among multiple H-bonds from n = 1–3. A trend of proton transformation exists from the hydroxyl to the N atom, which finally results in the cleavage of
the origin intramolecular H-bond and the formation of a new intramolecular H-bond between the amino and the O atom of TA.
Therefore, the most stable TA-(H2O)3 complex becomes a zwitterionic complex rather than a neutral type. A many-body interaction analysis showed that the major
contributors to the binding energies for complexes are the two-body energies, while three-body energies and relaxation energies
make significant contributions to the binding energies for some complexes, whereas the four-body energies are too small to
be significant. 相似文献
10.
S. Aime Mauro Botta Mauro Fasano Simonetta Geninatti Crich Enzo Terreno 《Journal of biological inorganic chemistry》1996,1(4):312-319
The non-covalent interaction between human serum albumin (HSA) and DOTA-like Gd(III) complexes containing hydrophobic benzyloxymethyl
(BOM) substituents has been thoroughly investigated by measuring the solvent proton relaxation rates of their aqueous solutions.
The binding association constants (K
A) to HSA are directly related to the number of hydrophobic substituents present on the surface of the complexes. Furthermore,
an estimation of ΔH° and ΔS° has been obtained by the temperature dependence of K
A. Assays performed with the competitor probes warfarin and ibuprofen established that the complexes interact with HSA through
two nearly equivalent binding sites located in the subdomains IIA and IIIA of the protein. Strong relaxation enhancements,
promoted by the formation of slowly tumbling paramagnetic adducts, have been measured at 20 MHz for complexes containing two
and three hydrophobic substituents. The macromolecular adduct with the latter species has a relaxivity of 53.2±0.7 mM–1 s–1, which represents the highest value so far reported for a Gd(III) complex. The temperature dependence of the relaxivity for
the paramagnetic adducts with HSA indicates long exchange lifetimes for the water molecules dipolarly interacting with the
paramagnetic centre. This is likely to be related to the formation, upon hydrophobic interaction of the complexes with HSA,
of a clathrate-like, second-coordination-sphere arrangement of water molecules. Besides affecting the dissociative pathway
of the coordinated water molecule, this water arrangement may itself significantly contribute to enhancement of the bulk solvent
relaxation rate.
Received: 6 November 1995 / Accepted: 17 April 1996 相似文献
11.
Miriam Altstein Tal Gabay Orna Ben-Aziz Shai Daniel Irina Zeltser Chaim Gilon 《Invertebrate neuroscience : IN》1999,4(1):0033-0040
The binding of [3H]tyrosyl-PBAN28-33NH2 to pheromone gland membranes of the moth Heliothis peltigera was investigated. The study describes the development of a pheromone biosynthesis-activating neuropeptide (PBAN) radioreceptor
assay and demonstrates the presence of a putative PBAN binding site on the pheromone gland. It also describes synthesis of
a radioligand and optimization of binding conditions with respect to membrane preparation, number of gland equivalents, kinetics
of ligand binding and composition of the binding solution. Binding was found to be optimal when membranes were freshly prepared
from frozen glands, incubated at a concentration of one gland equivalent per reaction tube in the presence of 10 mM HCO3
− ions. Equilibrium of ligand binding was obtained after 20 min. Presence of other components such as NaCl, KCl or SH reagents
did not have any effect on binding. Binding was found to be saturable, with a Kd of 5.73 ± 1.05 × 10−6 M and a Bmax of 1.85 ± 0.22 nmol/mg protein. Binding was effectively displaced by unlabeled PBAN1-33NH2 and PBAN28-33ΝΗ2 with a Ki of 4.3 ± 1.1 × 10−6 M and 4.9 ± 2.6 × 10−6 M, respectively.
Accepted: 4 February 1999 相似文献
12.
Cancer is a significant world health problem for which efficient therapies are in urgent demand. c-Src has emerged as an attractive
target for drug discovery efforts toward antitumor therapies. Toward this target several series of c-Src inhibitors that showed
activity in the assay have been reported. In this article, 3D-QSAR models have been built with 156 anilinoquinazoline and
quinolinecarbonitrile derivative inhibitors by using CoMFA and CoMSIA methods. These studies indicated that the QSAR models
were statistically significant with high predictabilities (CoMFA model, q
2 = 0.590, r
2 = 0.855; CoMSIA model, q
2 = 0.538, r
2 = 0.748). The details of c-Src kinase/inhibitor binding interactions in the crystal structure of complex provided new information
for the design of new inhibitors. As a result, docking simulations were also conducted on the series of potent inhibitors.
The flexible docking method, which was performed by the DOCK program, positioned all of the inhibitors into the active site
to determine the probable binding conformation. The CoMFA and CoMSIA models based on the flexible docking conformations also
yielded statistically significant and highly predictive QSAR models (CoMFA model, q
2 = 0.507, r
2 = 0.695; CoMSIA model, q
2 = 0.463, r
2 = 0.734). Our models would offer help to better comprehend the structure-activity relationships that exist for this class
of compounds and also facilitate the design of novel inhibitors with good chemical diversity. 相似文献
13.
The influence of ammonia on the anaerobic degradation of peptone by mesophilic and thermophilic populations of biowaste was
investigated. For peptone concentrations from 5 g l−1 to 20 g l−1 the mesophilic population revealed a higher rate of deamination than the thermophilic population, e.g. 552 mg l−1 day−1 compared to 320 mg l−1 day−1 at 10 g l−1 peptone. The final degree of deamination of the thermophilic population was, however, higher: 102 compared to 87 mg NH3/g peptone in the mesophilic cultures. If 0.5–6.5 g l−1 ammonia was added to the mesophilic biowaste cultures, deamination of peptone, degradation of its chemical oxygen demand
(COD) and formation of biogas were increasingly inhibited, but no hydrogen was formed. The thermophilic biowaste cultures
were most active if around 1 g ammonia l−1 was present. Deamination, COD degradation and biogas production decreased at lower and higher ammonia concentrations and
hydrogen was formed in addition to methane. Studies of the inhibition by ammonia of peptone deamination, COD degradation and
methane formation revealed a K
i (50%) for NH3 of 92, 95 and 88 mg l−1 at 37 °C and 251, 274 and 297 mg l−1 at 55 °C respectively. This indicated that the thermophilic flora tolerated significantly more NH3 than the mesophilic flora. In the mesophilic reactor effluent 4.6 × 108 peptone-degrading colony-forming units (cfu)/ml were culturable, whereas in the thermophilic reactor effluent growth of only
5.6 × 107 cfu/ml was observed.
Received: 24 April 1998 / Received revision: 26 June 1998 / Accepted: 27 June 1998 相似文献
14.
Ki Hwan Kim Irina Gaisina Franck Gallier Denise Holzle Sylvie Y. Blond Andrew Mesecar Alan P. Kozikowski 《Journal of molecular modeling》2009,15(12):1463-1479
Molecular modeling and docking studies along with three-dimensional quantitative structure relationships (3D-QSAR) studies
have been used to determine the correct binding mode of glycogen synthase kinase 3β (GSK-3β) inhibitors. The approaches of
comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) are used for the
3D-QSAR of 51 substituted benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3β inhibitors. Two binding modes of the inhibitors
to the binding site of GSK-3β are investigated. The binding mode 1 yielded better 3D-QSAR correlations using both CoMFA and
CoMSIA methodologies. The three-component CoMFA model from the steric and electrostatic fields for the experimentally determined
pIC50 values has the following statistics: R2(cv) = 0.386 nd SE(cv) = 0.854 for the cross-validation, and R2 = 0.811 and SE = 0.474 for the fitted correlation. F (3,47) = 67.034, and probability of R2 = 0 (3,47) = 0.000. The binding mode suggested by the results of this study is consistent with the preliminary results of
X-ray crystal structures of inhibitor-bound GSK-3β. The 3D-QSAR models were used for the estimation of the inhibitory potency
of two additional compounds. 相似文献
15.
Jose Neptuno Rodriguez-Lopez Andrew T. Smith R. N. F. Thorneley 《Journal of biological inorganic chemistry》1996,1(2):136-142
Horseradish peroxidase isoenzyme C (HRPC) mutants were constructed in order to understand the role of two key distal haem
cavity residues, histidine 42 and arginine 38, in the formation of compound I and in substrate binding. The role of these
residues as general acid-base catalysts, originally proposed for cytochrome c peroxidase by Poulos and Kraut in 1980 was assessed for HRPC. Replacement of histidine 42 by leucine [(H42L)HRPC*] decreased
the apparent bimolecular rate constant for the reaction with hydrogen peroxide by five orders of magnitude (k
1 = 1.4×102 M–1s–1) compared with both native-glycosylated and recombinant forms of HRPC (k
1 = 1.7×107 M–1s–1). The first-order rate constant for the heterolytic cleavage of the oxygen-oxygen bond to form compound I was estimated to
be four orders of magnitude slower for this variant. Replacement of arginine 38 by leucine [(R38L)HRPC*] decreased the observed
pseudo-first-order rate constant for the reaction with hydrogen peroxide by three orders of magnitude (k
1 = 1.1×104 M–1s–1), while the observed rate constant of oxygen bond scission was decreased sixfold (k
2 = 142 s–1). These rate constants are consistent with arginine 38 having two roles in catalysing compound I formation: firstly, promotion
of proton transfer to the imidazole group of histidine 42 to facilitate peroxide anion binding to the haem, and secondly,
stabilisation of the transition state for the heterolytic cleavage of the oxygen-oxygen bond. These roles for arginine 38
explain, in part, why dioxygen-binding globins, which do not have an arginine in the distal cavity, are poor peroxidases.
Binding studies of benzhydroxamic acid to (H42L)HRPC* and (R38L)HRPC* indicate that both histidine 42 and arginine 38 are
involved in the modulation of substrate affinity.
Received: 21 July 1995 / Accepted: 27 November 1995 相似文献
16.
Anwen M. Krause-Heuer William S. Price Janice R. Aldrich-Wright 《Journal of chemical biology》2012,5(3):105-113
The interactions of three platinum(II)-based anticancer complexes [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)]2+, [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)]2+, and [(5,6-dimethyl-1,10-phenanthroline)(1,2-diaminoethane)platinum(II)]2+ (56MEEN) with BSA have been examined by circular dichroism (CD), fluorescence and 1H pulsed gradient spin–echo (PGSE) diffusion NMR spectroscopy. The number of association constants and sites differed depending upon the spectroscopic method. This may be because each technique monitors different types of interaction/s and/or as a consequence of the different concentration ranges required for each technique. The titration of BSA with the achiral 56MEEN as monitored by CD indicates a reduction in the α-helical nature of the albumin, with the association constant calculated to be ~5 × 106 M−1 for one site. Due to the chiral nature of the other two complexes, their association with albumin was not monitored using CD but was examined using fluorescence and PGSE diffusion NMR. Titration of BSA with any of the three metal complexes resulted in quenching of fluorescence, with the number of association sites calculated to be ~1.1, with an association constant of ~2 × 105 M−1. PGSE diffusion NMR provided insights into interactions occurring with the BSA in its entirety, rather than with individual regions. Metal complex binding sites were estimated (~10 equivalent) from the diffusion data, with the average association constant for all sites ~102–103M−1. These experiments highlight the information that can be elucidated from complementary spectroscopic techniques and demonstrate the usefulness of PGSE diffusion NMR in monitoring multiple weak binding sites, which is of great importance in studying drug-biomolecule interactions. 相似文献
17.
Delta-endotoxin production by a strain of Bacillus thuringiensis subsp kurstakion complex media based on crude gruel and fish meal was investigated. High proteolytic activities were concomitantly produced
with the bioinsecticide. In such complex media, the repressive regulation due to readily consumed carbon sources was partially
overcome. In order to improve substrate assimilation, 0.5 g L−1 sodium chloride and 0.1% Tween-80 were supplemented to the production medium, increasing delta-endotoxin yields when using
gruel concentrations below 59 g L−1. At and beyond 75 g L−1 gruel, delta-endotoxin yields were not affected in the presence of 0.5 g L−1 NaCl and 0.1% Tween-80, but proteolytic activity yields were remarkably reduced. Thus, the use of sodium chloride and Tween-80
allowed reduction of the initial gruel concentration to 42 g L−1 for the production of 3350 mg L−1 delta-endotoxin, while it was only 3800 mg L−1 with 92 g L−1 gruel. Moreover, similar to 0.5 g L−1 NaCl and 0.1% Tween-80, the use of 10 g L−1 sodium acetate significantly improved delta-endotoxin production and also reduced the proteolytic activity to 250 U ml−1.
Received 05 November 1998/ Accepted in revised form 19 August 1999 相似文献
18.
Nicola D’Amelio Luca Fontanive Fulvio Uggeri Furio Suggi-Liverani Luciano Navarini 《Food biophysics》2009,4(4):321-330
Caffeine complexation by chlorogenic acid (3-caffeoylquinic acid, CAS Number [327-97-9]) in aqueous solution as well as caffeine–chlorogenate
complex in freshly prepared coffee brews have been investigated by high-resolution 1H-NMR. Caffeine and chlorogenic acid self-associations have also been studied and self-association constants have been determined
resorting to both classical isodesmic model and a recently introduced method of data analysis able to provide also the critical
aggregation concentration (cac). Furthermore, caffeine–chlorogenate association constant was measured. For the caffeine, the
average value of the self-association constant determined by isodesmic model (K
i = 7.6 ± 0.5 M−1) is in good agreement with the average value (K
a = 10 ± 1.8 M−1) determined with the method which permits the determination of the cac (8.43 ± 0.05 mM). Chlorogenic acid shows a slight
decreased tendency to aggregation with a lower average value of association constants (K
i = 2.8 ± 0.6 M−1; K
a = 3.4 ± 0.6 M−1) and a critical concentration equal to 24 ± 1 mM. The value of the association constant of the caffeine–chlorogenate complex
(30 ± 4 M−1) is compatible with previous studies and within the typical range of reported association constants for other caffeine–polyphenol
complexes. Structural features of the complex have also been investigated, and the complex conformation has been rediscussed.
Caffeine chemical shifts comparison (monomeric, complexed, coffee brews) clearly indicates a significant amount of caffeine
is complexed in beverage real system, being chlorogenate ions the main complexing agents. 相似文献
19.
Helma M. Prinssen Carla F. M. Molthoff René H. M. Verheijen Tim J. Broadhead Peter Kenemans Jan C. Roos Quentin Davies Arjan C. van Hof Malcolm Frier Wim den Hollander Abraham J. Wilhelm Terry S. Baker Mark Sopwith E. Malcolm Symonds Alan C. Perkins 《Cancer immunology, immunotherapy : CII》1998,15(1):39-46
mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted
effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a
split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1 mg/kg unlabelled hCTM01,
1 h before receiving 0.1 mg/kg 111In-labelled hCTM01 (100 MBq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues
and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to
its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits
6 days p.i. was 11.1 times higher than in normal tissues (P<0.0001) and 5.9 times higher than in blood (P<0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody.
The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic
agents to patients with ovarian cancer.
Received: 12 February 1998 / Accepted: 30 April 1998 相似文献
20.
Payot S Guedon E Desvaux M Gelhaye E Petitdemange E 《Applied microbiology and biotechnology》1999,52(5):670-674
The nutritional and physiological factors affecting sporulation of Clostridium cellulolyticum were studied using steady-state continuous cultures grown in both complex and synthetic media. Under cellobiose limitation,
the probability that cells will sporulate appears to be directly related to the growth rate. In complex medium, the highest
percentage of sporulation was 20% at a dilution rate of 0.015 h−1 whereas in synthetic medium it was 10% at 0.035 h−1. In both media, when the dilution rate was either higher or lower the percentage of sporulation decreased by between 2% and
4%. At low dilution rates, endospore formation was repressed under cellobiose-sufficient concentrations, suggesting catabolite
repression by cellobiose. Furthermore, the concentration of ammonium was important in determining the percentage of sporulation,
as ammonium limitation induced extensive sporulation at low growth rates even in an excess of cellobiose. The sporulation
process is not triggered when cells are cellobiose-exhausted both in complex and synthetic media. These data suggest that,
in C. cellulolyticum, an exogenous supply of carbon is required throughout the sporulation process. In the experimental conditions used in this
work, no relationship between glycogen accumulation or glycogen mobilization and endospore formation was detected in C. cellulolyticum.
Received: 15 April 1999 / Received revision: 15 June 1999 / Accepted: 22 June 1999 相似文献