Nathaniel I. Berlin

Life Span of Red Blood Cell

N. I. Berlin, T. A. Waldmann, and S. M. Weissman, “Life Span of Red Blood Cell” Page 588, line 23, volume 39, should read: (see pdf) Page 594, line 3, volume 39, should read: (see pdf)

Hematologic and biochemical studies in a case of lead poisoning

Abstract Detailed hematologic and biochemical studies in a patient with lead poisoning demonstrate that the potential life span of red cells produced under these circumstances is normal. A shortened mean red cell survival results entirely from the random destruction of some cells. The reduced half-life (T12) of chromium-labeled red cells in this condition is shown to result both from hemolysis and from an increased rate of edition of chromium from the tagged cells. The hemolytic effect of lead is a direct effect on mature red blood cells, which occurs independently of the effects of lead on heme biosynthesis in erythroid precursors. Treatment with EDTA rapidly reverses the latter but not the former. Although lead is an inhibitor of heme biosynthesis in vitro, the presence of both an increased rate of effective erythropoiesis and an increased early labeled peak indicates that heme biosynthesis may be increased in the lead-poisoned patient.

THE INFLUENCE OF BILIRUBIN ON OXIDATIVE PHOSPHORYLATION AND RELATED REACTIONS IN BRAIN AND LIVER MITOCHONDRIA: EFFECTS OF PROTEIN‐BINDING

1. The uncoupling of oxidative phosphorylation of liver mitochondria by bilirubin does not occur in the presence of equimolar quantities of human serum albumin. With brain mitochondria, however, albumin was not protective.

Direct measurement of the rates of synthesis of plasma proteins in control subjects and patients with gastrointestinal protein loss.

The guanido carbon of hepatic arginine is the common precursor of urea and of the arginine of plasma proteins synthesized in the liver. It is possible to measure the momentary synthetic rates of plasma proteins by pulse labeling this arginine pool with bicarbonate-(14)C. In the current study, this method has been adapted in order to use urinary urea data and was applied to control subjects and patients with gastrointestinal protein loss. The assumptions required for this determination are discussed. There was close agreement between albumin synthetic rates measured by this method and albumin catabolic rates derived from simultaneous albumin-(131)I studies, supporting the validity of the method and suggesting that there is relatively little fluctuation in the rate of albumin synthesis from time to time. The albumin synthetic rates in six control subjects averaged 5.8 mg/kg per hr, while those of five patients with gastrointestinal protein loss averaged 7.2 mg/kg per hr. Thus in these patients, there was relatively little acceleration of albumin synthesis in response to continued loss of plasma proteins into the gastrointestinal tract. Fibrinogen synthetic rates averaged 1.9 mg/kg per hr in five control subjects and 3.2 mg/kg per hr in five patients with gastrointestinal protein loss. Transferrin synthetic rates exhibited considerable individual variation in both groups and averaged 0.24 mg/kg per hr in four control subjects and 0.31 mg/kg per hr in five patients with gastrointestinal protein loss. The method employed in this study offers several advantages in studying plasma protein metabolism. It provides a direct measurement of protein synthesis, applicable to several proteins simultaneously, does not require a long-term steady state in the metabolism of the proteins, and is capable of measuring short-term fluctuations in synthetic rates. Therefore, this approach is applicable to the investigation of the physiological factors controlling the rates of synthesis for plasma proteins.

The Application of Multicompartmental Analysis to Problems of Clinical Medicine: Combined Clinical Staff Conference at the National Institutes of Health

Abstract This combined Clinical Staff Conference presents the mathematical basis and the investigational techniques and tools of compartmental analysis in the study of calcium, bilirubin, and immun...

Quantitative studies of the delivery of hepatic-synthesized bilirubin to plasma utilizing δ-aminolevulinic acid-4-14C and bilirubin-3H in man

After the simultaneous intravenous administration of unconjugated bilirubin-(3)H and delta-aminolevulinic acid-4-(14)C, the plasma disappearance curves of unconjugated bilirubin-(3)H and the plasma appearance curves of biosynthesized unconjugated bilirubin-(14)C have been defined in seven patients, three of whom had acute intermittent porphyria (AIP). The incorporation of (14)C into plasma unconjugated bilirubin, derived by an analysis which involves deconvolution of the two plasma curves, varied between 13.1 and 23.5% (mean 19.3%) of the injected dose in the nonporphyric patients and between 5.4 and 13.6% (mean 8.3%) of the injected dose in the porphyric patients. In five of the patients, the stercobilin-(14)C specific activity in a pooled specimen of feces was measured, enabling the following further values to be calculated: (a) the total (14)C radioactivity incorporated into bilirubin (21.0 and 25.3% [mean 23.2%] of the injected dose in two of the nonporphyric patients and between 8.5 and 25.3% [mean 14.2%] of the injected dose in the porphyric patients), and (b) the proportion of hepatic synthesized bilirubin delivered directly to plasma in the unconjugated form (between 0.520 and 0.904; mean for nonporphyric patients 0.712; mean for porphyric patients 0.614). The results demonstrate that a large proportion of bilirubin derived from hepatic hemes passes through the plasma in the unconjugated form before conjugation and secretion into bile.

Comparison of fecal urobilinogen excretion with bilirubin production in normal volunteers and patients with increased bilirubin production

Abstract The amount of bilirubin produced daily was determined from analysis of the plasma disappearance curve of unconjugated [14C]bilirubin in 13 healthy volunteers and 12 patients with a reduction in the red blood cell 51Cr half-life and/or increased bilirubin production. Simultaneous measurement of the fecal urobilinogen excretion made possible a determination of the fraction of the daily bilirubin production excreted in the feces as urobilinogen. In the normal volunteers an average of 92% of the injected isotope was recovered in the feces, indicating that bilirubin and its degradation products are excreted almost exclusively in the feces. Nevertheless, only 50% of the daily bilirubin production was recovered as fecal urobilinogen. Although the bilirubin production rates (mg/kg/day) were not significantly different in males and females, females excreted a significantly smaller fraction of the bilirubin produced as fecal urobilinogen. Because of the variable relationship between bilirubin production and fecal urobilinogen excretion, 4 of the 12 subjects with increased bilirubin turnover had “normal” values for fecal urobilinogen excretion.

Assay of hepatic glucuronyl transferase activity using [14C]bilirubin as substrate

Abstract A method for the assay of hepatic glucuronyl transferase activity using [ 14 C]bilirubin as substrate has been developed. Under the conditions of the assay, the conjugation products from normal rats and guinea pigs have been found to react with diazo reagent to form azo-pigment B. Evidence is presented that liver from congenitally jaundiced (Gunn) rats can metabolize small quantities of bilirubin to diazo-negative metabolites that were not characterized. This method is applicable to the quantities of enzyme derived from the small amounts of liver such as might be obtained in human liver biopsy samples.