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201.
RA Wallace JP Haar DB Miller SR Woulfe JA Polta KP Galen MR Hynes K Adzamli 《Canadian Metallurgical Quarterly》1998,40(5):733-739
A nonaromatic, small-molecule, gadolinium(3+)-chelate code named MP-2269 was synthesized and evaluated in animals as a potential MR contrast agent for blood pool. The ligand of MP-2269 was prepared by conjugating a lipophilic, albumin-binding moiety, 4-pentylbicyclo[2.2.2]octane-1-carboxylic acid, to an amino-functionalized DTPA derivative by means of a diaspartic acid linker. Proton relaxometry studies in vitro yielded spin-lattice relaxivities (R1) for MP-2269 of 6.2, 20.0 and 26.1 mM(-1)sec(-1) in water, rabbit blood, and human blood, respectively. The enhanced relaxivities in blood indicate significant binding of the agent to blood proteins. At a dose of 45 micromol/kg, MP-2269 showed a biphasic rabbit blood clearance profile with half-lives of 4.7 and 142 minutes, respectively, for the fast and slow components. In rats, the agent is cleared predominantly through the hepatobiliary pathway (approximately 70% in 24 h by this mode). The LD50 value of MP-2269 is approximately 3.0 mmol/kg in mice. Preliminary MR angiograms obtained in the rabbit showed excellent enhancement of blood vessels. Hence, MP-2269 has potential for future exploitation as a contrast agent for MR angiography. 相似文献
202.
KP Hopfner H Brandstetter A Karcher E Kopetzki R Huber RA Engh W Bode 《Canadian Metallurgical Quarterly》1997,16(22):6626-6635
The coagulation factors IXa (fIXa) and Xa (fXa) share extensive structural and functional homology; both cleave natural substrates effectively only with a cofactor at a phospholipid surface. However, the amidolytic activity of fIXa is 10(4)-fold lower than that of fXa. To identify determinants of this poor reactivity, we expressed variants of truncated fIXa (rf9a) and fXa (rf10a) in Escherichia coli. The crystal structures of fIXa and fXa revealed four characteristic active site components which were subsequently exchanged between rf9a and rf10a. Exchanging Glu219 by Gly or exchanging the 148 loop did not increase activity of rf9a, whereas corresponding mutations abolished reactivity of rf10a. Exchanging Ile213 by Val only moderately increased reactivity of rf9a. Exchanging the 99 loop, however, dramatically increased reactivity. Furthermore, combining all four mutations essentially introduced fXa properties into rf9a: the amidolytic activity was increased 130-fold with fXa substrate selectivity. The results suggest a 2-fold origin of fIXa's poor reactivity. A narrowed S3/S4 subsite disfavours interaction with substrate P3/P4 residues, while a distorted S1 subsite disfavours effective cleavage of the scissile bond. Both defects could be repaired by introducing fXa residues. Such engineered coagulation enzymes will be useful in diagnostics and in the development of therapeutics. 相似文献
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DNA probes specific to the Escherichia coli genes encoding Lon protease and RcsA hybridized to specific DNA sequences in a number of different microorganisms. Antiserum to either E. coli protein Lon or RcsA reacted with specific proteins in these organisms. These results provide structural evidence of the presence of Lon and RcsA in organisms other than E. coli. 相似文献
206.
Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism 总被引:1,自引:0,他引:1
MB Yaffe M Schutkowski M Shen XZ Zhou PT Stukenberg JU Rahfeld J Xu J Kuang MW Kirschner G Fischer LC Cantley KP Lu 《Canadian Metallurgical Quarterly》1997,278(5345):1957-1960
Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization. 相似文献
207.
L Kóbori MJ van der Kolk KP de Jong PM Peeters IJ Klompmaker T Kok EB Haagsma MJ Slooff 《Canadian Metallurgical Quarterly》1997,27(5):890-893
BACKGROUND/AIMS: The purpose of the study was to investigate the incidence of and risk factors for splenic artery aneurysms in liver transplant patients. METHODS: Medical records and the pre- and 1-year postoperative angiograms of 337 liver transplant patients were reviewed to assess the presence and characteristics of these aneurysms. RESULTS: Forty-five patients with aneurysms were identified (13%): 41 cases in 242 adult patients (17%) and four (4%) in 95 children (p<0.01). The female-to-male ratio was 2:1. The majority of the aneurysms (87%) were located in the distal third of the splenic artery and the majority (87%) of the patients presented multiple aneurysms. In patients without portal hypertension no aneurysms were identified, whereas in 16% of the patients with portal hypertension aneurysms were found (p<0.001). In adult patients the incidence of splenic artery aneurysms was significantly higher in patients with parenchymal diseases than in patients with cholestatic diseases (p<0.0001). Two patients (4%) died due to rupture of the aneurysms. Control angiographies, 1 year after liver transplantation, showed no changes in size and number of the aneurysms, and no new aneurysms were identified. CONCLUSIONS: The incidence of splenic artery aneurysms in liver transplant patients is 13%. They are generally multiple and located in the distal third of the splenic artery. The incidence is higher in women and in patients with parenchymal liver disease and portal hypertension. The incidence of rupture was 4%. 相似文献
208.
AIM: The incidence of functional autonomous adenomas, detected in every second nodular goiter by scintigraphic methods is very high in an area of iodine deficiency. The color-coded Doppler sonography (CCDS) as a diagnostic tool in differentiating thyroid nodules is discussed controversially. METHODS: In this prospective study we investigated the value of CCDS in 200 patients with nodular thyroid alterations compared with 99m-Technetium (Tc) scintigraphy. RESULTS: Focal maximas of Tc-uptake were detected in 22.5% of all patients, and 44.5% of the thyroid nodules showed increased vascularity. There was no correlation between nodular vascularity and thyroid 99m-Tc uptake (TcTU). In contrast to this we could demonstrate a significant relation between vascularity and the diameter of the nodule (p < 0.0001). The results are discussed in the context of method specific limitations of ultrasound examinations. CONCLUSION: Our results confirm that CCDS has no great importance in the differentiation of thyroid nodules. Scintigraphy remains the diagnostic method of choice to assess the topographic thyroid function. 相似文献
209.
KP Cockerham C Pal B Jani A Wolter JS Kennerdell 《Canadian Metallurgical Quarterly》1997,104(6):914-917
Experiments are carried out on 3400 mice, irradiated in dose 8 Gy (LD97/30). beta-Ketoanalogs of adrenaline (adrenalone, 50-150 mumol/kg), m,p-dipivaloyladrenaline (20 mumol/kg) and phenylephrine (but at 2070 mumol/kg) have the high radioprotective effect (survival is 60-100%), beta-ketoanalogs of isoprenaline and m-benzoylphenylephrine have the middle RPE (50-60%). Their effective doses (except dipivaloyladrenalone) are considerably bigger (in 9-76 times), than beta-hydroxysubstances doses, but the toxicity of benzoylphenylephrone, dipivaloyladrenalone and especially adrenalone is by far lower (consequently in 3, 8, 2, 7 and 136 times). Therapeutic indexes of beta-ketosubstances achieve 35-100. 相似文献
210.