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991.
Nishikawa Makiya Hirabayashi Hideki Takakura Yoshinobu Hashida Mitsuru 《Pharmaceutical research》1995,12(2):209-214
Hepatic targeting of proteins utilizing the sugar-recognition mechanism was investigated in mice after intravenous injection. Five proteins with different molecular weights, i.e., bovine -globulins (IgG), bovine serum albumin (BSA), recombinant human superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and chicken egg white lysozyme (LZM), were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated proteins (Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM). The numbers of galactose residues were 38, 20, 11, 6, and 5 for Gal-IgG, Gal-BSA, Gal-SOD, Gal-STI, and Gal-LZM, respectively. All galactosylated proteins were dose-dependently taken up by the liver and the relative amount accumulated in the liver was decreased with an increase of the administered dose. At low doses (0.05 and 0.1 mg/kg), Gal-IgG, Gal-BSA, and Gal-SOD could be taken up by the liver up to more than 70–80% of dose within 10 min after intravenous injection, but the maximum amounts accumulated in the liver were approximately 40 and 30% of the dose for Gal-STI and Gal-LZM, respectively. Pharmacokinetic analysis revealed that the hepatic uptake clearance (CLliver) was quite different around the molecular weight of 32 kDa and correlated with the amount delivered to the liver; Gal-IgG, Gal-BSA, and Gal-SOD has a large CLliver that is close to the hepatic plasma flow rate (85 ml/hr), whereas those of Gal-STI and Gal-LZM were approximately 10 ml/hr at low doses. As for the total amount accumulated in the liver, high glomerular filtration rate of Gal-STI and Gal-LZM was also shown to cause insufficient delivery to the liver apart from being caused by their low CLliver. 相似文献
992.
B. Dussol S. Geider A. Lilova F. Léonetti P. Dupuy M. Daudon Y. Berland J.-C. Dagorn J.-M. Verdier 《Urological research》1995,23(1):45-51
Our aims were to analyze the protein composition of the organic matrix of urinary stones and to investigate the role of albumin in its constitution. Five different morphological types of stones were studied. Proteins extracted from the stone were submitted to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by immunoblotting with antibodies to 13 urinary proteins. Nine of the 13 proteins were found in all types of stone: human serum albumin (HSA), 1-acid glycoprotein (1-GP), 1-microglobulin (1-M), immunoglobulins (Igs), apolipoprotein A1 (apo-A1), transferrin (Tr), 1-antitrypsin (1-T), retinol-binding protein (RBP) and renal lithostathine (RL). The 2-microglobulin (2-M) was present only in calcium oxalate and uric acid stones. In contrast, ceruloplasmin, haptoglobin and Tamm-Horsfall protein (THP) were detected in none of them. Because HSA appeared as the major protein component in all stones, we wondered whether it might play a specific role in the constitution of the stone matrix. Association of HSA with urinary proteins that were present in stones was demonstrated by showing that proteins present in the matrix comigrated with HSA on gel filtration, whereas proteins that were absent did not. Moreover, HSA induced the binding of stone matrix proteins to an albumin-specific affinity column. Finally, we evidenced HSA binding to calcium oxalate monohydrate (COM) crystals in a solution similar to urine. It was concluded that (1) only a subset of urinary proteins is present in stone matrix, (2) the same proteins are found in all types of stones, (3) HSA shows significant affinity for several proteins of the matrix, but not for proteins absent from stones and, (4) HSA also displays significant affinity for COM crystals. 相似文献
993.
Nader Gordjani Rainer Burghard Dirk Müller Helga Mathäi Gunther Mergehenn Jekabs U. Leititis Matthias Brandis 《Pediatric nephrology (Berlin, Germany)》1995,9(4):419-422
The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary 1-microglobulin and 2-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary 1-microglobulin and 2-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary 1-microglobulin and 2-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated. 相似文献
994.
Parviz Ghadirian PhD Bryna Shatenstein Maurice Verdy Pavel Hamet 《European journal of epidemiology》1995,11(3):275-281
Elevated levels of plasma uric acid have been linked to increased risk of cardiovascular diseases and their complications. As dairy proteins have been found to decrease plasma uric acid without increasing glomerular filtration rate, a sample of postmenopausal women living in Montreal was studied to investigate the nature of this relationship. Participants (158 Roman Catholic nuns) were randomly assigned to one of two test diets for a period of four weeks: the dairy foods group (n=81) consumed approximately 30 grams of dairy protein daily and the dairy-free diet group (n=77) ate no dairy foods at all. Subjects completed two one-day food records, a core questionnaire and a dairy foods diet history; blood specimens were obtained, and blood pressure, height and weight were measured. Average nutrient intakes differed as a consequence of the test diets, with significantly greater intakes of protein, fat, saturated fat, monounsaturated fat, potassium and calcium (p<0.01) in the dairy group after the study period, and lower dietary levels of protein, cholesterol, calcium and retinol (p<0.01) in the dairy-free group. Plasma uric acid was unchanged after the dietary intervention in the dairy group, but increased by 7.8 µmol/1 (p=0.03) in subjects on the dairy-free diet; however, diastolic blood pressure decreased in response to calcium (=–22.9, SE=10.0,p=0.02) among those whose diet included dairy foods. The study results suggest that proteins of dairy origin may play a role in stabilising or lowering plasma uric acid, and that calcium or other components found in milk products may also reduce diastolic blood pressure. While these findings have implications for dietary prevention to decrease cardiovascular risk in postmenopausal women, further investigations should examine these mechanisms in men over the age of 50 to ascertain whether a similar response would occur. 相似文献
995.
Esa R. Korpi Garry Wong Hartmut Lüddens 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(4):365-373
Clozapine, an atypical neuroleptic, functionally antagonizes the -aminobutyric acid-induced chloride uptake via the main central inhibitory receptor, -aminobutyric acid type A (GABAA) receptor, in brain vesicles. GABAA antagonism by micromolar concentrations of clozapine is more efficient in rat cerebrocortical and hippocampal membranes than in cerebellar membranes, as evidenced by clozapine reversal GABA-inhibition of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding. A typical neuroleptic, haloperidol, failed to antagonize GABA in any of these brain regions, while the specific GABAA antagonist 2-(3-carboxy-2,3-propyl)-3-amino-6-p-methoxyphenylpyrazinium bromide (SR 95531) was efficient in all three brain regions. Clozapine action on [35S]TBPS binding was unaffected by the benzodiazepine receptor antagonist flumazenil. Clozapine inhibited the binding of [3H]muscimol and [3H]SR 95531 to the GABA recognition site, but this effect only partially correlated with the regional differences in and the potency of clozapine antagonism of GABA-inhibition of [35S]TBPS binding, suggesting that also other than GABA sites may mediate clozapine actions. Autoradiography of [35S]TBPS binding revealed GABA antagonism by clozapine in most brain regions. Main exceptions were cerebellar granule cell and molecular layers, olfactory bulb external plexiform and glomerular layers and primary olfactory cortex, where clozapine antagonized GABA inhibition less than average, and lateral hypothalamic and preoptic areas where its antagonism was greater than average. Recombinant 622 receptors, the predominant 6 subunit-containing receptor subtype in cerebellar granule cells, failed to show GABA antagonism by clozapine up to 100 M. In contrast, recombinant 122 receptors, forming the predominant receptor subtype in the brain, were clozapine sensitive. Recombinant 622 and 632 receptors resulted in clozapine-insensitive receptors, whereas 612 receptors were clozapine sensitive. The efficacy of clozapine to antagonize GABA in 1x2 receptors decreased in the order of 112>122>132. The results indicate that clozapine antagonizes the function of most GABAA receptor subtypes, and that the interaction is determined by the interaction of the and subunit variants. GABA antagonism is a unique property of clozapine, not shared by haloperidol, which might be involved in the pharmacological mechanism for the increased seizure susceptibility associated with clozapine treatment. 相似文献
996.
Elisabetta Ciani Tiziana Guarnieri Antonio Contestabile 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,98(3):421-430
The excitotoxins kainic acid and N-methyl d-aspartate (NMDA) were unilaterally injected in the rat striatum. Kainic acid injections resulted in a widespread pattern of Fos protein induction, mainly involving cortical olfactory structures and hippocampus. Immunoreactive cells were observed in large number 2–24 h after injection and had almost completely disappeared by 48 h. NMDA injections elicited a shorter (2–8 h) expression of Fos protein, involving a lower number of cells in cortical olfactory structures, a much larger number of cells in the other cortical regions, and not involving the hippocampus at all. Characteristically none of the two excitotoxins stimulated Fos expression from striatal neurons, even in the close vicinity of the needle tract. In addition to striatal lesions almost equivalent in size, the two excitotoxins caused distant lesions of different extension: kainic acid resulted in extensive neuronal degeneration in the olfactory-entorhinal cortices and among pyramidal neurons of the hippocampus; NMDA caused a less widespread neurodegeneration, restricted to the olfactory cortex. Administration of the competitive NMDA antagonist CGP 39551 largely prevented the distant, but not the local, neuropathological changes caused by intrastriatal kainic acid or NMDA. The expression of Fos protein, however, was partially prevented only in NMDA cases. The present results show a good relationship between the spreading of circuit overexcitation caused by the two excitotoxins and the regional and temporal patterns of Fos expression. The relationship between Fos expression and neuropathological condition remains, however, elusive. 相似文献
997.
Rainer Netzer Pascal Pflimlin Gerhard Trube 《Pflügers Archiv : European journal of physiology》1994,426(3-4):206-213
The barium current through voltage-dependent calcium channels was recorded from cultured rat cortical neurons with the whole-cell configuration of the patch-clamp technique. The maximal current evoked by depolarising pulses from –80 mV to 0 mV was divided into inactivating and non-inactivating fractions. During the first minutes of whole-cell recording, the amplitude of the inactivating fraction increased from less than 0.1 nA to an average value of 1 nA, whereas the amplitude of the non-inactivating component remained essentially the same. This increase in amplitude was prevented when the perforated-patch technique was used, suggesting that some intracellular factor that inhibited the barium current was lost or destroyed during conventional whole-cell experiments. When GTP[-S] or GTP was added to the pipette solution, no increase or only a weak rise of the inactivating current was seen, whereas GDP[-S] accelerated its increase. The results suggest that some of the calcium channels expressed in cultured cortical neurons are inhibited by a G protein even in the absence of added neurotransmitter. The current increase observed during whole-cell recordings may be due to a loss of intracellular GTP and the subsequent inactivation of an inhibitory G protein. 相似文献
998.
本文采用SDS—PAGE法,测定7例健康育龄男子在肌肉注射十一酸睾酮(TU)前,用药后l、2、3个月及停药后精子计数恢复正常时的精浆蛋白浓度和组份变化,并结合血清测定激素水平及常规精液分析,以探讨TU对上述指标的影响及其相互关系。结果显示:用药早期精浆总蛋白浓度开始逐步降低,在停药后精子计数恢复正常时仍未达到正常水平。精浆总蛋白浓度的变化与精子活动率、前向运动率及LH呈正相关(r值分别为0.8975、0.7776、0.6406,P<0.01或0.05)。精浆蛋白组份也发生变化,其中51KD、37KD的蛋白条带变化最为明显,其变化除与精子活动率相关外(r=0.9094,P<0.01),其中51KD蛋白条带的变化还与精子前向运动率相关(r=0.7660,P<0.05)。上述结果提示TU可能在抑制生精之前即通过改变精浆蛋白而影响精子的功能,说明单用睾酮(T)的避孕机理是多因素的。 相似文献
999.
N-端融合蛋白对重组HBeAg抗原性的影响 总被引:1,自引:0,他引:1
目的 研究 N- 末端融合蛋白对大肠杆菌中表达的 H Be Ag 抗原性的影响。方法 用 P C R 法,从抗- H Bc( + ) 血清标本中获得 H B V Pre c - c 基因片段,将其插入质粒 Trc99 A,重组成亚克隆 P H B I。以 P H B I为模板,扩增获得编码乙肝病毒核心蛋白1 ~140 氨基酸的基因片段,加上终止信号,分别插入质粒p G E X- 2 T 和 Trc99 A 中,各自转化后,以 I P T G 诱导,大肠杆菌表达插入基因。以 E L I S A 和 S D S- P A G E 方法测定表达产物的分子量和 H Be Ag 、 H Bc Ag 滴度。结果 在 I P T G 诱导下,大肠杆菌中分别表达 N- 端融合的 G S T- H Be Ag 融合蛋白和非融合 H Be Ag 蛋白。分子量各为41000 D 和15000 D。培养裂解物经 E L I S A 测定,融合蛋白 H Be Ag : H Bc Ag 的滴度比为256 :1 ,非融合蛋白为16 :1 。结论 N- 端融合蛋白 G S T- H Be Ag 抗原性更接近血清 H Be Ag 。 相似文献
1000.
采用高效液相凝胶色谱法(GC-HPLC)、醋酸纤维膜电泳和半微量定氮法测定50%声振人血白蛋白空气微球制剂中球壁蛋白的含量。GC-HPLC确证了球壁蛋白主要成分为人血白蛋白;醋酸纤维膜电泳测定空气人血白蛋白微球制剂中人血白蛋白纯度>90%;半微量定氮法测出球壁蛋白含量平均值为3.56%左右,99%正常值范围为2.52%-4.60%。 相似文献