Eugene A. Johnson

Circadian System Phase — An Aspect of Temporal Morphology; Procedures and Illustrative Examples

Anatomists and histologists, among many other biologists, often find that a given variable studied by them undergoes changes with time; they are dealing with a so-called time function, a term that implies merely that a given value depends, at least in part, upon the time when it is sampled.

Susceptibility rhythm to E. coli endotoxin and bioassay.

Summary Light-synchronized periodicity analysis reveals a susceptibility rhythm in C mice to E. coli endotoxin. Susceptibility varies predictably and significantly along the 24-hour time scale. A dose of endotoxin which is compatible with survival of most animals when given during middle of daily dark period is highly lethal when it is given 8-12 hours earlier or later. LD50 also was determined for 2 samples from identical batch of endotoxin tested 12 h apart on separate groups of comparable C mice kept under conditions standardized for periodicity analysis: Differences in potency significant at 1% were seen at 2 dose levels common to both assays, the computed “potency ratio” being 3.22.

The electroencephalogram of elderly subjects revisited

The EEGs of 98 elderly volunteers were compared with those of 84 patients with a recent cerebral infarction who had achieved a stable clinical course. All subjects were uniformly evaluated according to a special protocol. The elderly volunteers were accepted for the study if they had no history, signs or symptoms of central nervous system disease. The EEGs were found to be significantly different between the two groups of subjects in several aspects. These included not only possible abnormalities, focal or diffuse, but also some normal features, such as alpha frequency and responses to photic stimulation and to hyperventilation. Groups of these differentiating features were analyzed. Using the single variable of ER (evoked response), discrimination of 80% was achieved. The variables that distinguish the volunteers from the patients may be used in the future to determine whether they are helpful in differentiating normals from patients with conditions other than stroke.

Circadian periodicity, adrenal corticosteroids, and the eeg of normal man.

Human EEG activity in the conventional frequency range of 1-30 c/s is a well-established entity. This paper illustrates a method for utilizing a conventional EEG frequency analyser to demonstrate a considerably lower frequency, circadian (about 24-h) rhythm in the EEGs of a group of human volunteers. This periodicity persists even in a group of totally sleep deprived (50 h) subjects. Plasma cortisol levels from blood samples drawn simultaneously with the EEG data also demonstrate circadian periodicity, and EEG-cortisol temporal (phase) relationships are apparent by inspection of the data collected, but could not be confirmed statistically. Evidence for the statistical significance of circadian organization of the EEGs and adrenal cortices of healthy men is provided by a phase testing technique developed for this study and discussed further in the appendix. This technique is readily applicable to further studies of periodicity in physiological functions.

Comparison of the distribution and binding of monoclonal antibodies labeled with 131-iodine or 111-indium

The distribution of two monoclonal antibodies with reactivity against human leukemia/lymphoma associated antigens (BA-1 antibody) and carcinoembryonic antigen (202 antibody) when labeled with 131I or 111In was studied in normal Balb/c mice. The BA-1 antibody of the IgM subclass was labeled with 131I by the micro iodine monochloride method at a 12:1 molar ratio and with 111In by the cyclic DTPA anhydride method at a 10:1 molar ratio. In vitro, the 131I-labeled BA-1 antibody bound 35.5% to 107 KM-3 leukemic cells while the 111In-labeled BA-1 antibody bound 29.9% to the same number of KM-3 cells. In vivo, the 111In-labeled BA-1 antibody showed a higher accumulation in liver, spleen, and kidney than the 131I-labeled BA-1 antibody. The 202 antibody of the IgG1 subclass was labeled with 131I at a 5:1 molar ratio and with 111In at a 7:1 molar ratio. In vitro, the 131I-labeled 202 antibody bound 30.9%, 27.4%, and 30.0% to 107 CO-112, WIDR, and LS-174T colon cancer cells, respectively. The 111In-labeled 202 antibody bound 20.5%, 30.2%, and 33.6%, respectively to the same number of colon cancer cells. In vivo, the 131I-labeled 202 antibody showed a higher tissue to blood ratio in liver, spleen, and kidney than the 111In-labeled 202 antibody. The data indicate that the relative distribution of 131I-labeled versus 111In-labeled monoclonal antibody may depend on the immunoglobulin subclass of the antibody and the molar ratio used in labeling.

Formation of bile acids in man: Metabolism of 7α-hydroxy-4-cholesten-3-one in normal subjects with an intact enterohepatic circulation

The formation of bile acids in man is thought to involve a series of reactions in which the initial steps are the same for both cholic acid and chenodeoxycholic acid. The point of bifurcation of the pathway is postulated to occur after the formation of 7alpha-hydroxy-4-cholesten-3-one. To test the hypothesis that the entire synthesis of both bile acids proceeds through this intermediate we studied the metabolism of labeled 7alpha-hydroxy-4-cholesten-3-one in eight normal subjects with an intact enterohepatic circulation. If all the production of cholic acid and chenodeoxycholic acid takes place via 7alpha-hydroxy-4-cholesten-3-one, the areas under the specific decay curves of cholic acid and chenodeoxycholic acid should be identical following a single injection of this labeled intermediate. However, in 6 of the 8 subjects studied the area under the cholic acid specific activity decay curve was significantly less than the area under the chenodeoxycholic acid specific activity decay curve. These results that the production of cholic acid in man may not always involve the intermediate 7alpha-hydroxy-4-cholesten-3-one.

Cerebral Circulation Studies Using Inhaled 133-Xenon and the Gamma Camera

Inhaled 133-xenon was utilized in conjunction with the Anger gamma scintillation camera to evaluate cerebral circulation in 20 asymptomatic control subjects and in 41 patients with clinical cerebrovascular disease. Sequental cerebral scintiphotos thus obtained revealed focal areas of decreased activity in 2 of 19 control subjects and in 15 of 38 patients. A computerized curve-fitting technique was used to calculate an index of cerebral blood flow (“K”) by means of the 133-xenon clearance curves obtained from each half of the head. Shorter periods of 133-xenon inhalation resulted in more rapid rates of clearance. In patients with clinical cerebrovascular disease, cerebral clearance rates tended to be lower and to show more variation between the two sides of the head than in asymptomatic subjects.

The Relative Biological Effectiveness of Cobalt-60 Gamma Rays and 220-Kvp X-Rays on the Viability of Chicken Eggs

The relative bioloical effectiveness of cobalt-60 gamma rays and 220- kvp x rays on the viabtlity of fertile chicken eggs has been determined. The RBE with 95% cofnidence interval was found to be 0.82 plus or minus 0.06 when the absorbed dose was measured at the position of the embryo. On the basis of absorbed dose rate determined at the center of the egg, the RBE was found to be 0.80 plus or minus 0.06. The relative biological effectiveness was found to be independent of dosage in the range from 330 to 1030 rads. The LD/sub 50/s for cobalt-60 gamma rays and 220-kvp x rays were found to be 705 plus or minus 21 and 583 plus or minus 17 rads, respectively. These values were determined from measurements of absorbed dose at the position of the embryo. (auth)

341 NOTE: Some Distribution-Free Properties of the Asymptotic Variance of the Spearman Estimator in Bioassays

SUMMARY In this paper, some distribution-free properties of the asymptotic variance of the Spearman estimator in Bioassay are investigated. It is shown that for various shapes of the tolerance distribution, the asymptotic variance of the Spearman estimator can be expressed approximately in terms of either the standard deviation or the distance between the 5th and the 95th percentile of the tolerance distribution. These distribution-free properties can be used in planning quantal assays of required precision.