The glomerular mesangium: kinetics using radiolabeled ferritin and the effects of aggregated IgG

A quantitative method for studying glomerular mesangial kinetics using radiolabeled native ferritin (125I-NF) is described. Groups of Sprague-Dawley rats were given injections of monomeric 125I-NF in a dose of 10 mg/100 g and sacrificed at 4, 16, and 36 hr. Radioactivity was measured in preparations of isolated glomeruli, spleen, and liver, and in blood. After initial uptake, a progressive decrease in the concentration of 125I-NF was observed in the mesangium and other organs. To examine the effect of one macromolecule on the mesangial kinetics of NF a separate group of animals was given aggregated human IgG (AHIgG) (40 mg/100 g) 4 hr prior to administration of 125I-NF. The administration of AHIgG did not alter the kinetics of 125I-NF in the mesangium, plasma, or spleen but the disappearance of 125I-NF from the liver was accelerated. Although the cellular mechanisms for uptake of NF and AHIgG are different, the presence of one macromolecule (AHIgG) within the mesangium did not affect the uptake and disappearance of another (NF). Thus, the glomerular mesangium has a relatively high capacity under normal circumstances.     

Radiolabeling, stability, and body distribution in rats, of low molecular weight polylactide homopolymer and polylactide-polyethyleneglycol copolymer

In order to study its fate in vivo, a low molecular-weight polylactide homopolymer was derivatized with a p-methoxyphenyl moiety, so as to make it susceptible to radiolabeling with 125I. A low molecular weight polylactide-polyethyleneglycol copolymer capped with ap-methoxyphenyl residue was also synthesized. The derivatized polymers were successfully [125I]iodinated in organic medium. The radiolabeled products were freed from [125I]iodide by dialysis and shown to be stable for 24 h on incubation at 37 degrees C in buffered saline or in blood. On longer incubation at 37 degrees C in buffered saline the radiolabeled polylactide released [125I]iodide and [125I]iodinated 3-(p-methoxyphenyl)propionic acid. The radiolabeled copolymer was more stable on incubation at 37 degrees C in buffered saline, but some [125I]iodide was released. The tissue distribution of radioactivity was determined 5 min, 1, 5 and 24 h after injecting male rats with 125I-labeled homopolymer or copolymer. Intravenous, intraperitoneal and subcutaneous injection routes were employed. Further rats were injected with [125I]iodide, to aid interpretation of the data. After administration of labeled homopolymer, a high concentration of radioactivity was found in the liver tissue. The levels slowly decreased over 24 h, and the polymer was successively found in the small and large intestine and the faeces. This is probably indicative of excretion via the bile. Concurrently radioactivity was excreted in the urine. After administration of labeled copolymer, a high concentration of radioactivity was found in the liver and the residual soft tissue, the latter fraction containing two-thirds of the radioactivity one hour after injection. The precise tissue location that this result indicates was not identified. After 1 h radioactivity was excreted in the faeces, again probably via the bile, and in the urine. Tissue distributions after intraperitoneal or subcutaneous injections were concordant with the above results and interpretations, with the additional factor of slow clearance from the injection site.     

Further studies of the metabolism of thyroxine and 3,5,3′-triiodothyronine in the guinea-pig

1. Thyroxine labelled with (125)I and triiodothyronine labelled with (131)I have been administered simultaneously to guinea-pigs and their metabolism studied by whole body counting and measurement of radioactivity in urine, faeces, and blood.2. The half-life of triiodothyronine in the body is about 19 hr, significantly less than that of thyroxine (41 hr).3. After triiodothyronine administration, an unidentified iodinated compound appears in the blood which complicates the estimation of the half-life of this hormone by measurement of the radioactivity in peripheral blood.4. A previous report, based on measurements of blood radioactivity, that the half-lives of the two hormones are similar in the guinea-pig was not confirmed.     

Intravascular circulation and distribution of human 51Cr-DBBF stroma-free hemoglobin, 51Cr-plasma, 51Cr-saline, 59FE-plasma, and 125I-albumin in the mouse

Male B6C3HF1 mice were infused with human 51Cr-labeled DBBF (bis 3,5-dibromosalicyl fumarate) crosslinked stroma-free hemoglobin (SFH). In the first hour following SFH infusion, 11.2% of the infused radioactivity was found in the skin, 11.4% in muscle, 9.1% in the skeleton, and 5% in the liver. Twenty-four hours after infusion, 15.4% of the radioactivity was found in the skin, 10.3%, in the muscle, 16.6% in the skeleton, and 6.7% in the liver. The circulation and distribution of 51Cr-labeled DBBF-SFH were compared with levels of 51Cr labeled plasma, 51Cr in saline, 59Fe labeled plasma, and 125I albumin. The radioactivity in the blood was similar for 51Cr-DBBF-SFH, 51Cr-plasma, and 59Fe-plasma. During the 24-hour post-infusion period, extravascular distribution of the 51Cr-saline, 51Cr-plasma, and 125I albumin within the organs was similar to that of 51Cr-DBBF-SFH, with the highest levels being in skin, muscle, skeleton and liver, and no increase in the levels in the lung or spleen. The distribution of 59Fe compared to that of 51Cr-DBBF, 51Cr-plasma, 51Cr-saline, and 125I albumin can be explained by the fact that 59Fe is utilized in the production of new red blood cells.     

Bovine serum albumin (BSA) nephritis in rats. IV. A sequential evaluation of mononuclear phagocyte system (MPS) function

A clearance kinetic study of intravenously administered 125I-labeled aggregated human IgG (125I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected 125I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was less than 0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of 125I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Serglycin secreted by leukocytes is efficiently eliminated from the circulation by sinusoidal scavenger endothelial cells in the liver

This study was undertaken to determine the fate of the circulating chondroitin sulfate proteoglycan serglycin. The human monocytic cell line THP-1 was cultured under serum-free conditions in the presence of [35S]sulfate. The conditioned medium was harvested and 35S-macromolecules were purified by Q-Sepharose anion-exchange chromatography and Superose 6 gel chromatography. After labeling with 125I, the purified material was treated with chondroitinase ABC and subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. A major band with mr of approximately 14 kDa appeared, consistent with the core protein of serglycin. The identity of the proteoglycan was confirmed by amino-terminal amino acid sequencing. Purified serglycin, labeled either with [35S]sulfate or 125I and fluorescein isothiocyanate, was injected intravenously into rats. The blood content of radiolabeled serglycin fell by 50% from 1 to 2.4 min after injection, indicating an initial t1/2 of 1.4 min or shorter. Approximately 90% of the recovered radioactivity was localized in the liver, 5% in the blood, and 5% altogether in urine, kidneys, and spleen about 30 min after injection. Isolation of liver cells at the same time point showed that 70% of the radioactivity was taken up by the sinusoidal scavenger endothelial cells, and 23 and 7% by the hepatocytes and Kupffer cells, respectively. When excess amounts of unlabeled hyaluronan was coinjected with radiolabeled serglycin, the elimination of serglycin was significantly inhibited, indicating that the hyaluronan receptor on the sinusoidal scavenger endothelial cells is responsible for the elimination of serglycin.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Retinol binding protein in plasma to evaluate the hepatotoxicity of rats treated with CCl4

Retinol binding protein (RBP) in plasma of rats treated with carbon tetrachloride (CCl4) was monitored to clarify if RBP is available for the evaluation of the drug-induced hepatotoxicity. Blood was withdrawn by heart puncture at 0 hr and 12 hr after i.p. administration of CCl4 (0.2 ml/kg) to rats. Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) in plasma significantly increased at 12 hr after CCl4 administration, compared with the control, while RBP in plasma significantly decreased. On the other hand, albumin in plasma was unaffected at 12 hr after CCl4 administration. Thus RBP seems to monitor the different aspects in the drug-induced hepatotoxicity from LDH and ALT, and from the viewpoint of protein synthesis in the liver, to be more sensitively affected by the drug-induced hepatotoxicity than albumin.     

Fate and biological action of human recombinant interleukin 1 beta in the rat in vivo

The plasma half life of recombinant human interleukin 1 beta (rhIL 1 beta) was determined in rats by measuring the disappearance of the radioactivity of 125I-labeled rhIL 1 beta from the circulation. The plasma clearance showed a biphasic behavior: an initial fast disappearance (half life of about 3 min) was followed by a second slower one (half life of about 4 h). Twenty minutes after a single-dose injection of 125I-labeled rhIL 1 beta most of the radioactivity was concentrated in kidneys, liver and intestine. rhIL 1 beta induced the synthesis of alpha 1-acid glycoprotein (AGP), alpha 1-cysteine proteinase inhibitor (CPI) and beta-fibrinogen mRNA in liver. Half maximal stimulation was elicited by approximately 3000 U of rhIL 1 beta per animal. The mRNA changes for AGP and CPI were followed by corresponding protein increases in serum. Twenty hours after rhIL 1 beta injection, serum AGP rose from 0.7 to 2.5 mg/ml. CPI increased from 0.3 to 1.9 mg/ml 25 h after administration of rhIL 1 beta. Within 20 h after rhIL 1 beta injection, albumin serum concentration showed a strong decrease, preceded by a reduction in hepatic albumin mRNA levels. Neither changes in albumin synthesis nor degradation can explain this decrease suggesting that other mechanisms such as increased transvascular permeability are involved.     

Macromolecular charge and reticuloendothelial function: comparison between the kinetics of administered native and cationized ferritins and the corresponding immune complexes in the mouse.

In order to evaluate the role of macromolecular charge on uptake by the reticuloendothelial system (RES), kinetic studies were carried out following the intravenous administration of 125I-labelled native ferritin (NF, pI 4.5) or cationized ferritin (CF, pI 7) to Swiss-Webster female mice subsequently killed at 2, 4, 8, 24 and 36 hr later. The same experiments were performed following the administration of radio-labelled (125I) native ferritin immune complexes (NFIC, pI 5-6.5) and cationized ferritin immune complexes (CFIC, pI 6.5-7.5). These complexes were prepared in five-times antigen excess by combination of affinity-purified anti-ferritin IgG-125I with NF or CF. A striking difference between the plasma clearance of NF and that of CF was observed in that the former was rapidly eliminated within 8 hr whereas the latter persisted in the circulation at 24 hr. This was associated with a significant increase in the uptake of NF by the liver, spleen, and kidney. No differences were observed in blood cell-associated radioactivity. Immunohistochemical studies confirmed the presence of increased amounts of NF in Kupffer cells and splenic phagocytes. Thus, the uptake of ferritin by components of the RES is highly dependent upon its pI. The present data may be explained by differences in diffusibility of CF and NF or alternatively by differential interactions with the cell surface in vivo. Contrary to the prior investigation carried out with the antigens alone, the plasma clearance and organ (liver, spleen and kidney) kinetic studies of NFIC and CFIC were similar. In addition, immunohistochemical studies demonstrated that the uptakes of NFIC (pI 5-6.5), CFIC (pI 6.5-7.5) and CFIC (pI 7-9) by Kupffer cells and splenic phagocytes were similar. As further confirmation for similarity in binding to Fc receptors of human polymorphonuclear leucocytes, Scatchard analysis failed to demonstrate any differences between NFIC and CFIC. These studies provide evidence that, within the range employed in this investigation, the charge of ferritin within the immune complex (and hence the charge of the complex itself) does not affect its uptake by receptors of phagocytic cells. In contrast, the uptake of ferritin, which is not Fc or C3 receptor dependent, is clearly conditioned by electrostatic charge.     

Pseudomonas aeruginosa Exotoxin in Mice: Localization and Effect on Protein Synthesis

We studied the fate of (125)I-labeled Pseudomonas aeruginosa (PA 103) exotoxin injected intravenously into mice and the effect of the exotoxin on the protein synthesis of various organs. After 2 h, only 5% of the injected label remained in the blood, in comparison with 30% of the injected control, consisting of [(125)I]bovine serum albumin. The highest concentration of radioactivity was consistently observed in the kidneys of toxin-treated mice. Lesser amounts of the label were found in the liver and the spleen. The heart, pancreas, lung, and brain showed very little uptake. Approximately 30% of the label (non-trichloroacetic acid precipitable) was recovered from the urine within 2 h after the injection. The behavior of [(125)I]toxoid was similar to that of the [(125)I]toxin. In contrast, in [(125)I]bovine serum albumin-treated mice, the label was uniformly distributed among the organs examined, and the concentration was low. After intravenous administration of the exotoxin, a 50% inhibition of protein synthesis was observed in the liver within 4 h, and virtually complete inhibition was observed shortly before the time of death. Kidney and spleen displayed slight reduction of protein synthesis at 2 to 4 h and approximately 50% reduction during the terminal stage. It appeared that the highest concentration of the toxin occurred in the kidney, where it was degraded, but its greatest toxic effect took place in the liver.     

The kinetics of chlorite and chlorate in rats

Chlorine dioxide (ClO2) is under consideration as an alternative to chlorination as a disinfectant for public water supplies. The primary products resulting from ClO2 disinfection of surface waters are chlorite (ClO2-) and chlorates (ClO3-). The kinetics of 36ClO2- and 36ClO3- was studied in rats. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of (0.17 microCi) 36ClO2- or (0.85 microCi) 36ClO3- orally; and 36Cl in plasma reached a peak at 2 hr and 1 hr, respectively. After 72 hr, radioactivity was highest in whole blood, followed by packed cells, plasma, stomach, testes, skin, lung, kidney, duodenum, carcass, spleen, ileum, brain, bone marrow and liver in 36ClO2- treatment. 36Cl excretion was greatest at 24 hr after the administration of 36ClO3-, but in the 36ClO2-, the excretion most likely represented saturation of the biotransformation and excretion pathways. About 40% of the total initial dose was excreted at 72 hr in the urine and feces in both treatments. No 36Cl was detected in expired air throughout the 72 hr studied.     

Ligandin and Z protein in binding of thyroid hormones by the liver.

Sephadex G-100 chromatography of rat liver supernatant after addition of [125I]T3 revealed four peaks of protein-bound radioactivity in the void volume, albumin, ligandin, and Z-containing regions, respectively. The peaks were identified by cochromatography of BSP and [125I]T3 and immonodiffusion with antiratligandin IgG and antirat Z IgG. Binding of [125I]T4 to rat liver supernatant occurred in void volume, albumin, and Z regions only. Studies in vivo reveal a pattern of [125I]T3 binding to rat liver supernatant fractions quantitatively different from that observed in vitro. [125I]T4 binding to liver supernatant fractions in vivo occurred in all four peaks. BSP or bilirubin added to liver supernatant decreased T3 and T4 binding by each fraction. Flavaspidic acid inhibited binding of T3 and T4 to albumin, ligandin, and Z protein. Phenobarbital pretreatment of rats increased binding of T3 by ligandin and of T4 by albumin-containing fractions. Circular dichroism studies with purified rat liver ligandin suggest that T3 and T4 bind competitively to the same site as does bilirubin; the association constants of T3 and T4 for ligandin are 10(6) and 10(5) M-1, respectively. T4 was bound only by purified ligandin and not by ligandin in liver supernatant. To determine whether unconjugated bilirubin interferes with hepatic uptake of T3, [125I]T3 was administered to icteric homozygous and phenotypically normal heterozygous Gunn rats. Hepatic uptake and supernatant binding [125I]T3 were significantly reduced in homozygous Gunn rats. Hepatic uptake of [125I]T3 was also reduced in vivo by infusion of BSP with or without flavaspidic acid. BSP infusion abolished [125I]T3 binding to ligandin; BSP and flavaspidic acid abolished binding to ligandin and Z. These observations suggest that ligandin and Z protein are thyroid hormone binding proteins in rat liver cytosol and may influence the net flux of iodothyronies from plasma into the liver.     

Relationship among altered glomerular barrier permselectivity, angiotensin II, and mesangial uptake of macromolecules

Clinical and experimental studies suggest that accumulation of phlogogenic macromolecules in the glomerular mesangium may lead to mesangial expansion and eventual glomerulosclerosis. In focal glomerulosclerosis and nephrotic syndrome entrapment of macromolecules is observed in areas of glomerulosclerosis. To determine whether mesangial uptake of radiolabeled, heat-aggregated IgG (AG125I), a biologically active macromolecular protein, is influenced by increased glomerular filtration barrier permeability, we evaluated the glomerular uptake of AG125I in three models of proteinuria: aminonucleoside of puromycin nephropathy (PAN), adriamycin nephropathy, and Heyman's nephropathy. Rats were studied approximately 1 week after onset of proteinuria. AG125I was measured in preparations of isolated glomeruli and compared to simultaneous blood, liver, and spleen levels. Only rats with PAN had a marked increase in glomerular AG125I compared to control rats, 7.8 versus 2.6 micrograms/mg of glomeruli, respectively. We then evaluated whether a continuous infusion of a competitive inhibitor of angiotensin II, saralasin (300 micrograms/kg of body weight/minute), influenced mesangial uptake of AG125I in PAN rats. Strikingly, glomerular AG125I in rats with PAN was reduced to levels comparable to that observed in control rats infused with only saralasin, 2.8 versus 3.0 micrograms/mg of glomeruli, respectively. This effect on glomerular AG125I content was independent of any significant effect of saralasin on blood, hepatic, or splenic levels of AG125I. Moreover, these changes in glomerular AG125I in saralasin-infused rats with PAN did not appear to directly correlate with changes in whole kidney function. These studies also demonstrated that proteinuria per se did not influence mesangial uptake of macromolecules. Thus, these data indicated that angiotensin II had an important effect on intraglomerular factors that modulate mesangial localization of phlogogenic macromolecules.     

胃癌单克隆抗体1D1-2在荷瘤裸鼠体内的放射免疫显像

本文应用人胃癌组织及细胞株移植建立了裸大鼠和裸小鼠两种胄癌移植模型。用~(125)I和~(131)I标记抗人胃癌单克隆抗体1D1-2,体外试验表明碘化1D1-2具有特异性的结合活性。注入荷瘤裸鼠体内72h后,显示该抗体高度浓集于肿瘤组织,浓聚指数为4.5,而正常组织仅为1.3,T/NT比分别为2～12倍,与胃组织比为3.2倍、放射免疫显像显示出清晰的肿瘤图像。提示单克隆抗体1D1-2应用于肿瘤定位诊断及导向治疗的可能性。     

131I标记重组人表皮生长因子在裸鼠体内的辐射生物学效应研究

研究131I标记的重组人表皮生长因子(131I-rhEGF)对荷人乳腺癌裸鼠的辐射生物学效应。通过131I-rhEGF在小鼠体内的分布实验找寻131I-rhEGF的主要浓聚组织,再通过生化检查和活组织病理检查检测131I-rhEGF对荷人乳腺癌裸鼠主要浓聚131I-rhEGF的组织的辐射损伤。131I-rhEGF在小鼠体内的分布实验显示,131I-rhEGF主要浓聚在肾、肝、脾、血。生化检查和活组织病理检查结果显示,注射131I-rhEGF2次(每次注射量相当于50kg人体注射14.58GBq,间隔为14d)对荷人乳腺癌裸鼠的肿瘤有较强的杀伤作用,而对肾、肝、脾和造血组织均无辐射损伤。因此,131I-rhEGF在受体介导放射性靶向治疗乳腺癌的过程中对正常组织是安全的药物。     

Degradation of immunoreactive albumin in young and old conscious female rats

The kinetics of inactivation of plasma albumin was studied in young (3-4 months) and old (25-28 months) Sprague-Dawley female rats. Conscious, free-moving animals carrying indwelling atrial and carotid cannulas received a single injection of [125I]-albumin (rat) via the carotid cannula. Sequential blood samples were removed at intervals during the following 120 min, and total (TR) and immunoprecipitable radioactivity (IPR) were determined in the corresponding plasmas. TR disappearance curves for young and old animals were almost identical but IPR disappearance curves showed a significantly faster decline in the young rats. The absolute plasma volumes for young and old rats were (mean +/- S.E.M.), 10.8 +/- 1.1 and 14.4 +/- 1.5 ml, respectively (P less than 0.05). The IPR/TR ratio, an estimate of albumin inactivation within the plasma space, showed a monoexponential decrease in vivo with a t 1/2 of 11.4 +/- 5.1 and 39.3 +/- 10.8 h (P less than 0.05) for young and old rats, respectively. The in vitro t 1/2s for albumin were 5.25 +/- 1.02 and 3.42 +/- 0.91 days (NS) for young and old rats, respectively. It is concluded that: the rate of albumin catabolism declines with age in the female rat; albumin is mainly inactivated in the extravascular space; and total plasma volume increases significantly with age in this species.     

Demonstration of antiinflammatory activity of fibrinogen and fibrinopeptides in rats

Carrageenin-induced inflammatory rat paw swelling was significantly inhibited by intraperitoneal injection of rat fibrinogcn. Whole-body radioscanning of the rat after intraperitoneal administration of 131I-labeled fibrinogen revealed the accumulation of radiolabeled material in the inflammed rat paw. Resorption studies showed that not more than 4% of the intraperitoneally administered [¹²⁵I]fibrinogen could be demonstrated in the peripheral blood. Furthermore only 1/3 of this circulating radiolabeled protein was able to take part in clot formation, suggesting that inhibition of edema formation is mediated by fibrinogen-derived split products. This is further supported by the finding that rat fibrinopeptides, released by the action of thrombin, also diminish edema formation both after intracardial and intraperitoneal injection into carrageenin-stimulated rats.     

Pharmacokinetics, subcellular distribution, and covalent binding of [3H]bleomycin in hamsters after intratracheal administration

Pharmacokinetics, subcellular distribution (SCD), and covalent binding of a single dose of 1 microCi of [S-methyl-3H]bleomycin ([3H]-BLM]) in combination with one unit of unlabeled bleomycin were studied in hamsters following intratracheal (IT) injection. The radioactivity decreased from the lung biexponentially with time. The apparent half-time of absorption for the alpha-phase was 1.1 and 17.9 hr for the beta-phase. The plasma disappearance curve of [3H]BLM fits to a two-compartmental model with the apparent half-life removal for the alpha-phase being 1.6 hr and for the beta-phase 116.9 hr. The radioactivity was detected in all studied tissues. The radioactivity from spleen, testicle, liver, fat, RBC, brain, adrenal, and kidney manifested only the alpha-phase of the disappearance curve, while the beta-phase was complicated by redistribution processes. Of the eight tissues, the spleen had the shortest (2.0 hr) and kidney the longest (12.1 hr), and the remaining tissues had half-lives which ranged from 4 to 10 hr. The SCD study revealed that 85 to 95% of the total radioactivity in the lung and liver homogenate was associated with the soluble fraction (SF) at 30 min after treatment, thereafter, the radioactivity from both tissues gradually decreased to 60% of the total at 24 hr. The SF of the lung homogenate had the highest specific radioactivity (SRA) of any of the fractions during the period between 0.5 and 6 hr. The SRA, however, decreased biexponentially and attained a value similar to that of the mitochondrial and microsomal fractions at 12 and 24 hr after treatment. In the case of liver, the SF had the highest, the nuclear the lowest, and mitochondrial and microsomal fractions the same level of SRA at 30 min. Thereafter, the SRA of all fractions were increased with time. A significant amount of radioactivity from [3H]BLM was covalently bound to lung, liver, and plasma proteins. The SF of the lung contained an increasing amount of radioactivity covalently bound after 1.5 hr of [3H]BLM injection and nearly all radioactivity measured in the plasma was covalently bound. It was concluded from the findings of this study that the presence of a major portion of [3H]BLM in the SF of the lung and its covalent linkage with the proteins of this fraction might initiate the complex sequence of events at the metabolic level necessary for the pneumotoxicity.     

The effect of diet and acute starvation on the deiodination of thyroxine and triiodothyronine in the thyroidectomized rat

1. General agreement exists that the level of thyroid function is depressed by starvation. The virtually complete cessation of biliary-faecal thyroxine loss in the starved animal makes the significance of this reduction difficult to assess in physiological terms.2. Deiodination of [(131)I]thyroxine was investigated in thyroidectomized rats. Thus central feed-back effects were eliminated and the changes in peripheral utilization of thyroxine could be observed. The simultaneous use of [(125)I] sodium iodide permitted changes in renal handling of iodide to be taken into consideration.3. Rats fed oxoid (Oxo Ltd. diet 41 B) deiodinated a significantly greater proportion of thyroxine in the 24 hr after injection of a tracer dose of [(131)I]thyroxine than did the starved or glucose-fed rat. [(131)I]triiodothyronine was also probably deiodinated at a faster rate in oxoid-fed rats than in starved or glucose-fed rats.4. Thyroxine was deiodinated at a faster rate by starved rats than by rats fed glucose.5. Thyroxine disappeared significantly faster from the blood in oxoid-fed than in the starved or glucose-fed rat. Thyroxine also disappeared faster from the blood in the starved rat than in the glucose-fed rat over 24 hr.6. These results are discussed in relation to previous findings of depressed pituitary-thyroid function in starvation.