The level of aberrant lymphocytes in the blood of rats and duration of survival after radionuclide incorporation

There is a positive correlation between the number of aberrant lymphocytes in the experimental rat blood, 24 h following the administration of 45Ca, 131I, 131I together with 90Sr, and 45Ca together with 137Cs, and the life span of exposed animals. It is suggested that the cytogenetic index should be used in the prognosis of the radionuclide-induced life span shortening.     

Effect of iodine-131 on the induction of osteosarcoma by strontium-90

The paper submits the results of estimation of the osteosarcomogenic effectiveness of 90Sr in a combination with 131I incorporated prior to or after the administration of 90Sr. It was demonstrated that the incidence of osteosarcomas increased in rats received 131I a weak after the administration of 90Sr.     

Efficient mutation induction by 125I and 131I decays in DNA of human cells

To examine the role of radiation energy deposition in DNA on cellular effects, we investigated the ability of 125IdUrd and 131IdUrd to kill cells and induce mutations at the hprt locus. We employed human lymphoblastoid cells proficient (TK6) or deficient (SE30) in the ability to incorporate a thymidine analog into DNA by way of the thymidine kinase (TK) scavenger pathway. Iodine-125 releases a shower of low-energy Auger electrons upon decay which deposit most of their energy within 20 nm of the decay site, whereas 131I is a high-energy beta/gamma emitter that is generally considered to emit sparsely ionizing radiation. Although 125IdUrd incorporated into cellular DNA was very effective at producing toxic and mutagenic effects in TK6 cells, virtually no effect was seen in TK-deficient cells incubated with similar levels of 125IdUrd in the extracellular medium. In response to 131IdUrd treatment, 0.45 X 10(-6) mutants were induced per centigray dose deposited within the nucleus in TK-proficient cells, whereas few mutations were induced in TK-deficient cells at doses up to 38 cGy from 131I decays occurring in the medium. The differences in biological response between TK6 and SE30 cells cannot be explained by differential radiosensitivity or IdUrd sensitization of the cell lines involved. We conclude that both 125I and 131I decays occurring while incorporated into DNA are more effective at inducing cell killing and mutations in human cells than either nonincorporated decays or low-LET radiations. These results suggest that localized energy deposition is an important factor in producing biologically important damage by both of these isotopes, and that residual lesions following the decay of DNA-incorporated radioisotopes may contribute to the toxic and mutagenic effects observed in TK-proficient cells. Furthermore, they emphasize that certain beta/gamma-emitting isotopes such as 131I may be particularly hazardous when incorporated into DNA.     

Trypsin inhibitor,mineral availability,and performance of broiler chickens fed on diets based on rice bran

Trypsin inhibitor in rice bran was inactivated by moist heat, but not by dry heating or treatments with 0.1% H₂SO₄, 0.1% NaOH or 0.1% NaCl. Heating rice bran could not improve its growth promotion value in the diet of broilers, which was related to the feed intake. Groundnut meal was the major protein supplement in the diets. Rice bran diets did not affect weight of pancreas (1.45–1.50 g/kg body weight). Use of ⁴⁵Ca revealed that availability of calcium on a rice bran diet was lower than on a maize-based diet. A similar effect on ⁵⁹Fe-availability was noted, although this result needs confirmation. Lack of differences in weight of thyroid glands and uptake of ¹³¹I by thyroids of birds on maize- and rice bran-based diets indicated the absence of any goitrogenic substance in the rice bran.     

Combined lesion in rats from 89Sr and 131I in their repeated uptake into the body

The results are submitted concerning the biological effect of 89Sr and 131I delivered separately and in a combination within a wide dose range. 89Sr has proved to be the major contributor to the effect observed. The effect produced by the radionuclides delivered in a combination was lesser than additive.     

Calcium and pancreatic beta-cell function. 4. Evidence that glucose and phosphate stimulate calcium-45 incorporation into different intracellular pools.

beta-Cell-rich pancreatic islets were microdissected from ob/ob-mice and used for studies of 45Ca uptake and washout. Irrespective of whether the experiments were performed at 21 or 37 degrees C both glucose and phosphate stimulated the net uptake of lanthanum-nondisplaceable 45Ca. The stimulatory effect of phosphate was additive to that produced by glucose. 45Ca incorporated in response to phosphate differed from that taken up in the presence of 20 mM glucose in being easily washed out although it was not affected by the glucose concentration of the washing medium. The efflux of 45Ca was reduced after introducing phosphate into a medium used to perifuse islets which had accumulated 45Ca in response to 20 mM glucose. This suggests that the outward calcium transport can be influenced also by intracellular trapping of the cation. The glucose-stimulated insulin release was inhibited by phosphate; an effect reversed by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. It is concluded that a common effect of glucose and phosphate is to trap calcium in the pancreatic beta-cells but that there are fundamental differences between their effects on intracellular distribution of calcium and on insulin release.     

吗啡和血管紧张素II对大鼠脑突触小体Ca^2＋摄取的拮抗效应

Behavioral observations have repeatedly shown that the analgesic effect of morphine can be antagonized by intracerebroventricular injection of angiotensin I (A I), although mechanisms underlying the action were obscure. Since a prevention of Ca2+ uptake into the nerve terminals was considered as one of the mechanisms for morphine analgesia, we examined the effect of A I and morphine on the 45Ca uptake by rat brain synaptosomal preparations. Morphine of 10(-8)-10(-6) mol/L produced a dose-related suppression on synaptosomal 45Ca uptake, which was completely reversed by the opioid antagonist naloxone of 10(-6) mol/L. A I of 10(-8)-10(-6) mol/L, on the contrary, enhanced 45Ca uptake. This effect was totally abolished by saralasin, a A I antagonist, at 10(-6) mol/L. When synaptosomal preparations were incubated in a mixture of morphine (10(-6) mol/L) and A I (10(-8)-10(-6) mol/L), the effect of morphine was almost completely reversed. The results suggest that the distinct effect of A I may account for, at least in part, the antagonistic effect of A I on morphine analgesia.     

Binding of acetylated low density lipoprotein and maleylated bovine serum albumin to the rat liver: one or two receptors?

The liver is the major organ involved in clearance of acetylated low density lipoprotein (acetyl-LDL) and maleylated serum albumin (Mal-BSA). Quantitative analysis of the hepatic uptake by sequential scintigraphy in rats shows that the hepatic uptake capacity for Mal-BSA is at least 15 times larger than for acetyl-LDL particles. A membrane-associated M approximately 250,000 daltons hepatic receptor for acetyl-LDL and Mal-BSA was 1450-fold purified from total membrane by Triton X-114 solubilization, chromatography on polyethylenimine cellulose and gel filtration. This receptor incorporated into liposomes displayed a saturable binding of [131I]Mal-BSA with a dissociation constant Kd = 15 nM and to [131I]acetyl-LDL with a dissociation constant Kd = 0.9 nM. The binding of both ligands was sensitive to poly(vinyl sulfate). The purified scavenger receptor system has a binding capacity for [131I]Mal-BSA 20 times larger than for [131I]acetyl-LDL. This is similar to the maximal removal capacity of the rat liver for both ligands in vivo. Binding studies with Mal-BSA, acetyl-LDL and anti-idiotypic receptor antibodies as competitors for [131I]Mal-BSA and [131I]acetyl-LDL binding demonstrate that [131I]Mal-BSA and [131I]acetyl-LDL compete for a common binding site. However, not all of the Mal-BSA binding sites are capable of interacting with acetyl-LDL.     

Effect of calcium, insulin and growth hormone on membrane fluidity. A spin label study of rat adipocyte and human erythrocyte ghosts

ESR spectra were recorded from rat epididymal adipocyte ghosts labeled with the 5-nitroxide stearic acid spin probe, I(12,3). Polarity-corrected and approximate order parameters, that are sensitive to the flexibility of the incorporated label, were used to evaluate the membrane lipid fluidity. Addition of CaCl2 a 37 degrees C decreased the fluidity, as indicated by positive increases in the order parameters. The ordering effect of Ca2+ was concentration-dependent, reached saturation at approx. 3--4 mM, and was completely reversed by excess EGTA. Previous studies indicated that low- and high-affinity sites on adipocyte plasma membranes are able to bind 45Ca2+, and our results suggest that Ca2+-induced alterations in the lipid fluidity involve cation binding to low-affinity sites. The cellular movements of Ca2+ and, in particular, the binding of Ca2+ to the plasma membrane may play important roles in insulin's action on fat cell function. The possibility that insulin directly alters the membrane fluidity was tested by adding hormone to freshly-prepared I(12,3)-labeled adipocyte ghosts. Insulin, at concentrations (10(-6) M) that enhance glucose uptake into intact adipocytes, did not affect the fluidity of ghosts suspended in buffers with or without Ca2+. The fluidities of I(12,3)-labeled rat adipocyte ghosts or human erythrocyte ghosts were also unaffected by various forms of human growth hormone.     

~(131)I-Herceptin对HER2过表达乳腺癌细胞Bcl-xL表达的影响

目的:探讨131I-Herceptin对HER2过表达乳腺癌细胞Bcl-x L表达的影响。方法:采用Iodogen法制备131I-Herceptin,超滤法纯化后测定其标记率、放射化学纯度和免疫结合率。通过免疫荧光法检测乳腺癌细胞表面HER2表达水平。131I(4.625 MBq/m L)、Herceptin(125μg/m L)及131I-Herceptin(4.625 MBq/m L)干预乳腺癌BT474细胞后,Western blot检测细胞中Bcl-x L的表达。结果:131I-Herceptin的标记率、放射化学纯度和免疫结合率分别为(89.71±2.93)%、(91.80±1.43)%和(58.84±3.35)%。BT474细胞膜表面HER2表达水平明显高于MDA-MB-231细胞。Herceptin、131I-Herceptin组BT474细胞内Bcl-x L表达水平明显低于对照组及131I组(均P0.01),而Herceptin与131I-Herceptin组之间细胞内Bcl-x L含量差异无统计学意义(P0.05)。结论:131I-Herceptin保留Herceptin对HER2过表达乳腺癌细胞Bcl-x L表达的抑制作用并促进细胞凋亡,进而与131I产生协同作用,较Herceptin更有效地杀伤HER2过表达乳腺癌细胞。     

Effect of parathyroid hormone on the transport of 45Ca2+ and 3H-GABA in nerve endings isolated from the rat cerebral cortex

Parathyroid hormone (PTH) (0.1-10 ng/ml) evokes a dose-dependent increase in 45Ca2+ accumulation in synaptosomes isolated from the rat brain cortex. In the presence of PTH the fast (I sec) potential-dependent 45Ca2+ uptake was less than in the control. PTH had no effect on 3H-GABA uptake by synaptosomes (P2 fraction). Synaptosomes preincubated in the presence of PTH in Ca2+-free medium and transferred into Ca2+-containing normal medium released more 3H-GABA than control synaptosomes. In this case depolarization-evoked 3H-GABA release was diminished.     

Uptake of 45-Calcium by Spirostomum ambiguum*

SYNOPSIS. Spirostomum ambiguum equilibrated with ⁴⁵Ca in the external medium after about 14 days under normal conditions. As the external Ca concentration was increased, uptake was increased but only until the internal concentration was ～ 60 mM. Changing the Ca/K ratio or increasing the K or Mg concentrations had no effect on uptake of the isotope; this was taken as an indication that most of the uptake reflected Ca binding as apatite. Increasing and decreasing the temperature increased and decreased Ca uptake, but Ca bound at higher temperatures remained in the animal at lower temperatures. Feeding caused a marked increase in uptake of isotope, probably due to the availability of a large number of binding sites on the products of digestion perhaps accompanied by increased permeability of the cell membrane. It is argued that most of the ⁴⁵Ca taken up is incorporated into Ca phosphate deposits, although it is likely that there will be a certain amount of free or weakly bound Ca.     

NLR、PLR与分化型甲状腺癌术后131I清甲效果的关系及其预测价值分析

摘要 目的：探讨中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）与分化型甲状腺癌（DTC）术后碘131（¹³¹I）清甲治疗效果的关系及对DTC术后¹³¹I清甲效果的预测价值。方法：选择2019年3月至2021年12月在江苏大学附属徐州医院行甲状腺切除术且术后进行¹³¹I清甲治疗的DTC患者150例为研究对象,根据¹³¹I清甲治疗效果分为清甲成功组（107例）和清甲未成功组（43例）,通过检查血常规获得中性粒细胞计数、血小板计数、淋巴细胞计数并计算NLR、PLR,比较两组NLR、PLR;采用单因素及多因素logistics回归模型分析¹³¹I清甲疗效的影响因素,采用受试者工作特征曲线（ROC）分析NLR、PLR对¹³¹I清甲治疗效果的预测价值。结果：清甲成功组NLR、PLR低于清甲未成功组（P＜0.05）,单因素分析显示清甲成功组促甲状腺激素（TSH）高于清甲未成功组,甲状腺球蛋白（Tg）水平低于清甲未成功组,清甲成功组病灶最大径小于清甲未成功组（P＜0.05）;多因素logistics回归分析显示,高NLR、PLR、Tg是¹³¹I清甲治疗失败的独立危险因素（P＜0.05）;NLR、PLR及联合检测预测¹³¹I清甲治疗效果的ROC曲线下面积（AUC）分别为0.760、0.732、0.829,NLR与PLR联合检测的AUC高于二者单独检测。结论：高NLR、PLR是DTC术后¹³¹I清甲未成功的独立危险因素,早期检测NLR、PLR对DTC术后¹³¹I清甲治疗效果具有较好的预测价值。     

On the origin of mitochondria: a reexamination of the molecular structure and kinetic properties of pyruvate dehydrogenase complex from brewer''s yeast

45Ca2+ incorporated in response to glucose was selectively mobilized from the beta-cell-rich pancreatic islets of ob/ob-mice after raising the intracellular Na+ by removal of K+ or addition of ouabain or veratridine. Also studies of insulin release indicated opposite effects of glucose and Na+ on the intracellular sequestration of calcium. The fact that glucose inhibits insulin release induced by raised intracellular Na+ indicates that this sugar can lower the cytoplasmic [Ca2+]. The concept of a dual action of glucose on the cytoplasmic [Ca2+]. The concept of a dual action of glucose on the cytoplasmic [Ca2+] might well explain previous observations of an inhibitory component in the glucose action on the 45Ca2+ efflux.     

Energetics of the induced structural change in a Ca2+ regulatory protein: Ca2+ and troponin I peptide binding to the E41A mutant of the N-domain of skeletal troponin C

Structural studies have shown that the regulatory domains of skeletal and cardiac troponin C (sNTnC and cNTnC) undergo different conformational changes upon Ca(2+) binding; sNTnC "opens" with a large exposure of the hydrophobic surface, while cNTnC retains a "closed" conformation similar to that in the apo state. This is mainly due to the fact that there is a defunct Ca(2+)-binding site I in cNTnC. Despite the striking difference, the two proteins bind their respective troponin I (TnI) regions (sTnI(115-131) and cTnI(147-163), respectively) in a similar open fashion. Thus, there must exist a delicate energetic balance between Ca(2+) and TnI binding and the accompanying conformational changes in TnC for each system. To understand the coupling between Ca(2+) and TnI binding and the concomitant structural changes, we have previously engineered an E41A mutant of sNTnC and demonstrated that this mutation drastically reduced the Ca(2+)-binding affinity of site I in sNTnC, and as a result, E41A-sNTnC remains closed in the Ca(2+)-bound state. In the present work, we investigated the interaction of E41A-sNTnC with the sTnI(115-131) peptide and found that the peptide binds to the Ca(2+)-saturated E41A-sNTnC with a 1:1 stoichiometry and a dissociation constant of 300 +/- 100 microM. The peptide-induced chemical shift changes resemble those of Ca(2+) binding to sNTnC, suggesting that sTnI(115-131) induces the "opening" of E41A-sNTnC. In addition, the binding of sTnI(115-131) appears to be accompanied by a conformational change in site I of E41A-sNTnC so that the damaged regulatory site can bind Ca(2+) more tightly. Without Ca(2+), sTnI(115-131) only interacts with E41A-sNTnC nonspecifically. When Ca(2+) is titrated into E41A-sNTnC in the presence of sTnI(115-131), the Ca(2+)-binding affinity of site I was enhanced by approximately 5-fold as compared to when sTnI(115-131) was not present. These observations suggest that the binding of Ca(2+) and TnI is intimately coupled to each other. Together with our previous studies on Ca(2+) and TnI peptide binding to sNTnC and cNTnC, these results allow us to dissect the mechanism and energetics of coupling of ligand binding and structural opening intricately involved in the regulation of skeletal and cardiac muscle contraction.     

Relationship between RNA synthesis and the Ca2+-filled state of the nuclear envelope store

RNA synthesis and ATP-dependent (45)Ca(2+) uptake were measured simultaneously in isolated nuclear fraction of rat liver nuclei. Maximal level of RNA synthesis was obtained under ATP-dependent (45)Ca(2+)-uptake conditions (1 microM free [Ca(2+)] and 1 mM ATP in the bathing solution). This experimental condition was defined as "stimulated nuclei" condition. ATP-dependent (45)Ca(2+) uptake was inhibited using different strategies including: (a) eliminating Ca(2+) (1 mM EGTA); (b) lowering the ATP concentration; (c) modifying nuclear envelope membranes Ca(2+) permeability (Ca(2+) ionophores); or (d) inhibiting the nuclear Ca(2+) pump (thapsigargin and 3',3',5',5'-tetraiodophenolsulfonephthalein). Under all the above conditions, RNA synthesis was lower than in "stimulated nuclei" condition. In the presence of ionomycin, RNA synthesis was significantly higher at 500 nM free [Ca(2+)], as compared with RNA synthesis in a Ca(2+)-free medium or at 1muM free [Ca(2+)]. However, even in such condition (500 nM free [Ca(2+)]), RNA synthesis was lower than RNA synthesis obtained in "stimulated nuclei" condition. We suggest two components for the effect of Ca(2+) on RNA synthesis: (A) a direct effect of nucleoplasmic [Ca(2+)]; and (B) an effect dependent on the accumulation of Ca(2+) in the nuclear envelope store mediated by the SERCA nuclear Ca(2+) pump.     

Calcium and pancreatic β-cell function: 4. Evidence that glucose and phosphate stimulate calcium-45 incorporation into different intracellular pools

β-Cell-rich pancreatic islets were microdissected from ob/ob-mice and used for studies of ⁴⁵Ca uptake and washout. Irrespective of whether the experiments were performed at 21 or 37°C both glucose and phosphate stimulated the net uptake of lanthanum-nondisplaceable ⁴⁵Ca. The stimulatory effect of phosphate was additive to that produced by glucose. ⁴⁵Ca incorporated in response to phosphate differed from that taken up in the presence of 20 mM glucose in being easily washed out although it was not affected by the glucose concentration of the washing medium. The efflux of ⁴⁵Ca was reduced after introducing phosphate into a medium used to perifuse islets which had accumulated ⁴⁵Ca in response to 20 mM glucose. This suggests that the outward calcium transport can be influenced also by intracellular trapping of the cation. The glucose-stimulated insulin release was inhibited by phosphate; an effect reversed by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. It is concluded that a common effect of glucose and phosphate is to trap calcium in the pancreatic β-cells but that there are fundamental differences between their effects on intracellular distribution of calcium and on insulin release.     

Ca2+ compartments in saponin-skinned cultured vascular smooth muscle cells

A method for saponin skinning of primary cultured rat aortic smooth muscle cells was established. The saponin-treated cells could be stained with trypan blue and incorporated more 45Ca2+ than the nontreated cells under the same conditions. At low free Ca2+ concentration, greater than 85% of 45Ca2+ uptake into the skinned cells was dependent on the extracellularly supplied MgATP. In the intact cells, both caffeine and norepinephrine increased 45Ca2+ efflux. In the skinned cells, caffeine increased 45Ca2+ efflux, whereas norepinephrine did not. The caffeine-releasable 45Ca2+ uptake fraction in the skinned cells appeared at 3 X 10(-7) M Ca2+, increased gradually with the increase in free Ca2+ concentration, and reached a plateau at 1 X 10(-5) M Ca2+. The 45Ca2+ uptake fraction, which was significantly suppressed by sodium azide, appeared at 1 X 10(-5) M Ca2+ and increased monotonically with increasing free Ca2+ concentration. The results suggest that the caffeine-sensitive Ca2+ store, presumably the sarcoplasmic reticulum, plays a physiological role by releasing Ca2+ in response to norepinephrine or caffeine and by buffering excessive Ca2+. The 45Ca2+ uptake by mitochondria appears too insensitive to be important under physiological conditions.     

Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving ¹³¹I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2–4 GBq of ¹³¹I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44–0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03–1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments.     

Biochemical changes of the liver in rats with a combined lesion from 89Sr and 131I

The results of the biochemical changes induced by 89Sr and 131I in a rat liver after their separate and combined administration within a wide range of doses are presented. Administered in a combination the radionuclides produced the additive effect when estimated by some indices, and more than additive, according to other tests.