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431.
Navin Reddy Gaik Lin Ong T. M. Behr Robert M. Sharkey David M. Goldenberg M. J. Mattes 《Cancer immunology, immunotherapy : CII》1998,46(1):25-33
We reported previously that the blood clearance of injected mouse IgG2a was extremely rapid in many strains of nude and nu/+ mice. In an attempt to determine the cause of this phenomenon, the levels of endogenous IgG2a in the blood of these mice
was assayed. It was found that the serum level of IgG2a was extremely low in many of these mice, below 50 μg/ml, which is
20–100 times lower than the expected normal value. Great heterogeneity between individual mice was observed in their blood
level of IgG2a, and there was an excellent correlation between low blood IgG2a levels and rapid clearance of injected IgG2a.
Thus, the blood IgG2a levels are so low that a novel, previously undescribed effect occurs, namely the rapid clearance of
small amounts of injected IgG2a. The clearance is due primarily to binding sites in the spleen and liver. The low level of
endogenous IgG2a is not due to the lack of a thymus, since it occurs in nu/+ as well as nude mice, but can probably be attributed to the very clean environment in which these mice are raised. In assays
of sera from approximately 50 mouse strains, low IgG2a levels were found in all nude colonies and also in some normal mouse
strains. Some nude mice displayed relatively normal IgG2a clearance rates despite having low levels of endogenous IgG2a. In
repeated bleedings of individual mice, IgG2a levels were found to fluctuate greatly. A similar clearance effect was observed
with a human IgG1 Ab injected into mice. This rapid clearance of injected IgG, of certain subclasses, represents a practical
problem for many experiments in which antibodies are used for diagnosis or therapy, and several methods of circumventing the
problem are discussed.
Received: 15 August 1977 / Accepted: 14 October 1997 相似文献
432.
温度、盐度和pH对马氏珠母贝稚贝清滤率的联合效应 总被引:2,自引:0,他引:2
清滤率(Clearance rate, CR)与滤食性贝类生长发育密切相关,采用Box-Behnken设计(BBD)和响应曲面法,在实验室条件下研究了温度(18-34℃)、盐度(20-40)和pH(6.5-9.5)对马氏珠母贝(Pinctada martensii)稚贝清滤率(CR)的联合效应,旨在建立温度、盐度和pH对马氏珠母贝稚贝清滤率的定量关系模型,并通过统计优化方法得出温度、盐度和pH的最佳组合。结果表明:温度的一次效应、温度和pH的互作效应、盐度和pH的互作效应以及温度、盐度和pH的二次效应对马氏珠母贝稚贝清滤率的影响均极显著(P<0.01);盐度的一次效应、pH的一次效应以及温度和盐度的互作效应对清滤率无显著影响 (P>0.05)。实验得出的清滤率模型决定系数为0.9950,预测决定系数为0.9284,表明该模型建立有效并可用于预测马氏珠母贝稚贝的清滤率。通过采用优化方法得出,在温度26.95℃,盐度29.69,pH8.09时,稚贝清滤率达到最大,最大值为1.4894×10-3L/h,满意度为0.9886。研究结果可为马氏珠母贝滤食生理研究及稚贝培育提供理论依据。 相似文献
433.
434.
Alison Betts Anne Keunecke Tamara J. van Steeg Piet H. van der Graaf Lindsay B. Avery Hannah Jones 《MABS-AUSTIN》2018,10(5):751-764
The linear pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs) can be considered a class property with values that are similar to endogenous IgG. Knowledge of these parameters across species could be used to avoid unnecessary in vivo PK studies and to enable early PK predictions and pharmacokinetic/pharmacodynamic (PK/PD) simulations. In this work, population-pharmacokinetic (popPK) modeling was used to determine a single set of ‘typical’ popPK parameters describing the linear PK of mAbs in human, cynomolgus monkey and transgenic mice expressing the human neonatal Fc receptor (hFcRn Tg32), using a rich dataset of 27 mAbs. Non-linear PK was excluded from the datasets and a 2-compartment model was applied to describe mAb disposition. Typical human popPK estimates compared well with data from comparator mAbs with linear PK in the clinic. Outliers with higher than typical clearance were found to have non-specific interactions in an affinity-capture self-interaction nanoparticle spectroscopy assay, offering a potential tool to screen out these mAbs at an early stage. Translational strategies were investigated for prediction of human linear PK of mAbs, including use of typical human popPK parameters and allometric exponents from cynomolgus monkey and Tg32 mouse. Each method gave good prediction of human PK with parameters predicted within 2-fold. These strategies offer alternative options to the use of cynomolgus monkeys for human PK predictions of linear mAbs, based on in silico methods (typical human popPK parameters) or using a rodent species (Tg32 mouse), and call into question the value of completing extensive in vivo preclinical PK to inform linear mAb PK. 相似文献
435.
Haibin Luo Yuling Li David Robbins Sheau-Chiann Wang Guoling Xi Matthew Cox Simone M. Nicholson Chenghong Wei Timothy M. Pabst William K. Wang 《Biotechnology progress》2021,37(3):e3119
Process-related impurities (PRIs) derived from manufacturing process should be minimized in final drug product. ICH Q3A provides a regulatory road map for PRIs but excludes biologic drugs like monoclonal antibodies (mAbs) that contain biological PRIs (e.g. host cell proteins and DNA) and low molecular weight (LMW) PRIs (e.g., fermentation media components and downstream chemical reagents). Risks from the former PRIs are typically addressed by routine tests to meet regulatory expectations, while a similar routine-testing strategy is unrealistic and unnecessary for LMW PRIs, and thus a risk-assessment-guided testing strategy is often utilized. In this report, we discuss a safety risk management strategy including categorization, risk assessment, testing strategy, and its integrations with other CMC development activities, as well as downstream clearance potentials. The clearance data from 28 mAbs successfully addressed safety concerns but did not fully reveal the process clearance potentials. Therefore, we carried out studies with 13 commonly seen LMW PRIs in a typical downstream process for mAbs. Generally, Protein A chromatography and cation exchange chromatography operating in bind-and-elute mode showed excellent clearances with greater than 1,000- and 100-fold clearance, respectively. The diafiltration step had better clearance (greater than 100-fold) for the positively and neutrally charged LMW PRIs than for the negatively charged or hydrophobic PRIs. We propose that a typical mAb downstream process provides an overall clearance of 5,000-fold. Additionally, the determined sieving coefficients will facilitate diafiltration process development. This report helps establish effective safety risk management and downstream process design with robust clearance for LMW PRIs. 相似文献
436.
Different formulae used in the literature for calculation of ingestion rates are reviewed. Their applicability is discussed in relation to two criteria: the occurrence of saturation of the feeding and/or growth of the food particles. It is shown by simulations that the differences in results obtained by calculating ingestion following a linear or an exponential model are restricted to a few percent. Calculation of ingestion rates by subtraction of particle concentrations from control and grazing bottles can result in substantial over- or underestimation depending on the growth constant of the food particles and the grazing time.The formule l=Vk(Czt–Czoekt)/N(l–ekt) is proposed for the calculation of ingestion rates under saturated circumstances.It is demonstrated that, with data obtained by multi-size class analysis, calculations on total particle concentrations are only feasible when growth constants and grazing coefficients are equal for all size classes considered.Attention is drawn to calculation problems resulting from non-normally distributed results and from non equal particle concentrations in control and grazing bottles at the beginning of the experiment. For the latter problem, two correction methods are proposed.Communication no. 327 of the Delta Institute for Hydrobiological Research. 相似文献
437.
Maggie J. Watson 《Journal of Field Ornithology》2012,83(4):407-411
ABSTRACT Collecting blood from neonatal or prehatched chicks is sometimes necessary, requiring specialized blood collection techniques and skills. However, such sampling can be difficult and could potentially have adverse effects. I developed a method for collecting blood from chicks still in an egg. The technique involves enlarging the pipping hole, removing the chick's head to take blood from a jugular vein, and returning the chick into its original position in the egg to complete hatching back in the nest. I used this technique on Crested Tern (Thalasseus bergii) chicks (N= 13), with no apparent adverse effects to growth or short‐term survival. The amount of blood extracted (0.1–0.15 ml) was sufficient for a blood smear, hematocrit, and total white blood cell count. This method should be useful for eggs as small as 40 mm in length; eggs smaller than this would likely not be good candidates for this technique because eggshells may be too thin to safely handle. This technique may be useful for investigators studying the immunological and endocrinological transition between embryos and hatchlings. 相似文献
438.
Richard E. Weller Janet F. Baer Carlos A. Mlaga Raymond L. Buschbom Harvey A. Ragan 《American journal of primatology》1992,28(2):115-123
The clearance and excretion of creatinine, calcium, phosphorus, sodium, and potassium by the kidney was evaluated in 62 owl monkeys using timed urine collections and quantitative urinalyses. The endogenous clearance of creatinine was determined for each monkey. Urinary electrolyte excretion and fractional electrolyte excretions (FE) were measured. Linear regression analysis was used to calculate the correlation between urinary excretion and FE for each electrolyte. The coefficient of determination for each analyte was significant (P ? .0001). Determination of FE was found to be an appropriate indicator of the renal handling of electrolytes and, when viewed in conjunction with urinalysis and other serum parameters, an aid in evaluating renal function in the owl monkey. © 1992 Wiley-Liss, Inc. 相似文献
439.
Kim L. Hossner Reinhart B. Billiar 《Biochimica et Biophysica Acta (BBA)/General Subjects》1979,585(4):543-553
Plasma kinetics and liver metabolism of iodanated human corticosteroid-binding protein have been studied in ovariectomized female rats. 125I-labeled human corticosteroid-binding globulin prepared by a modified chloramine T reaction was shown to be physically intact and biologically active. Intravenously injected 125I-labeled human corticosteroid-binding globulin was shown to give a complex clearance pattern from the plasma, with half-lives of 7.5 and 51 min. Estrogen injections had no effect on plasma clearance rate. Direct involvement of liver plasma membrane receptors for asialoglycoproteins in 125I-labeled human corticosteroid-binding globulin metabolism was demonstrated in vivo and in vitro using asialofetuin as a competitive inhibitor. 125I-labeled human asialo-corticosteroid-binding globulin was cleared from the plasma with a half-life of less than 1 min, while the simultaneous injection of 5 mg asialofetuin maintained the circulating plasma levels. Asialofetuin also slowed the clearance of intact 125I-labeled human corticosteroid-binding globulin from the plasma (). Binding of 125I-labeled human asialo-corticosteroid-binding globulin to rat liver plasma membranes in vitro was inhibited in a dose-dependent manner by asialofetuin, but not by intact human corticosteroid-binding globulin or fetuin. 125I-labeled human corticosteroid-binding globulin did not bind significantly to the membranes. It is concluded that human corticosteroid-binding globulin clearance from rat plasma is rapid and that the carbohydrate moiety of human corticosteroid-binding globulin is involved in its clearance and catabolism by the liver. 相似文献
440.