Leon S. Rosenblatt

Seasonal variation in immunity of humans

Abstract A whole blood lymphocyte stimulation test (using phytohemagglutinin and concanavalin‐A), an in vitro corollary of in vivo cell mediated immunity, was done with blood collected twice monthly from five male subjects over a period of 20 months (February 1979‐September 1980). Simple correlations between pairs of subjects were positive and, in general, statistically significant. For some subjects the data fit a harmonic function with an estimated peak activity in the winter of 1979, similar to our previous findings with dogs. The seasonal fluctuations were analyzed for possible association with 22 environmental parameters. Selected parameters were highly specific for each subject; however, parameters directly or indirectly associated with quality and quantity of solar radiation (e.g. sunspot numbers and number of minutes between sunrise and sunset) were often chosen as predictors of lectin‐induced lymphocyte transformation. No trend was observed in the correlation between environmental factors and imm...

Comparative studies on in vivo carcinogenesis in rats and in vitro mutagenesis of mutagenic coal fly ash

Polycarbonate filter packets containing either mutagenic coal fly ash or beeswax pellets with 210 μg 7,12‐dimethylbenz[a]anthracene (DMBA) were placed in the lumina of heterotopic rat trachea/ transplants for 1, 2, 4, and 6 mo to test for carcinogenicity. Release of DMBA, as calculated from spectrophotometric determination of residual DMBA in removed beeswax pellets, was found to approach first‐order kinetics. The release rate was estimated to be 45.02% per month of the amount remaining in the pellets. Histopathological examination demonstrated in DMBA‐exposed tracheas consistent hyperplastic, metaplastic, and neoplastic changes (squamous‐celt carcinoma) by 2 mo post‐transplantation, when only 20.5% of total DMBA remained in pellets. These histopathological changes were not found in tracheas exposed to packeted coal fly ash or other control samples including loose coal fly ash, packeted heat‐inactivated fly ash, packeted glass beads, or empty tracheas. Mutagenicity tests with Salmonella typhimurium TA1538...

Seasonal variations in lectin-induced lymphocyte transformation in beagle dogs.

Abstract The lymphocyte stimulation test (LST) is an in vitro corollary of in vivo cell‐mediated immunity. We have analyzed LST results from 32 dogs covering a 16‐month time span. Two mitogens (plant lectins) were used in the LST, phytohemagglutinin (PHA) and concanavalin A (Con A) with comparable results. All dogs exhibited a seasonal variation in LST results using both mitogens. The dogs were either controls or were in one of five groups that received whole‐body gamma ray irradiation from a 60CO source. There was little effect of irradiation except on the mean levels of oscillation. Few differences were noted among groups. The estimated mean times of peak activity in the LST ranged from July 19‐August 2 for PHA and from July 18‐August 15 for Con A. The times of peak of individual dogs for both mitogens were predominantly in the calendar quarter June 21 ‐September 20, and were, therefore, not randomly distributed throughout the year. The implications of these findings are discussed.

Sample Size for Estimating the Quantiles of Endothelial Cell-Area Distribution

The estimation of corneal endothelium mean cell area (and, hence, mean cell density) is an important problem in clinical ophthalmology. Mitotic division of these cells is not known to occur, and cell deaths are followed by the enlargement of adjacent cells. As a consequence, cell-area distributions change drastically as functions of age and disease. Changes in cell-area distributions, in particular multimodality and skewness due to aging, are observed, and give rise to some difficult sampling problems. In this paper, sample quantiles are investigated as an alternative to the use of the sample mean. Asymptotic approximations are provided for the sample sizes required to estimate population quantiles with a desired precision. Asymptotic sample sizes are then compared with those obtained from tolerance limits. Empirical sample quantiles that can be used as benchmarks to compare corneas of normal individuals against corneas with unknown cell-area distributions are also presented. Aspects that merit further investigation are noted.

Genotoxicity of the phosphoramidate agent tabun (GA)

Five mutagenicity tests were performed on Agent GA (Tabun, phosphoramidocyanidic acid, dimethyl-, ethyl ester) as part of a program to demilitarize chemical warfare agents. GA was mutagenic in Salmonella spp. assays with S-9 and it was a direct-acting mutagen to mouse lymphoma cells. GA did not promote unscheduled DNA synthesis in rat hepatocytes; it induced sister chromatid exchanges in mouse cells in vitro but in vivo. The conclusion that GA is a weakly acting mutagen is supported by the fact that it was mutagenic in only three of the five assays, and that increases in mutagenicity were often less than 2-fold the controls and occurred near toxic levels.

In vitro radiation response studies on bone marrow fibroblasts (CFU-F) obtained from normal and chronically irradiated dogs☆

The radiation resistance of bone marrow fibroblasts as measured by their proliferative potential was evaluated in chronically irradiated dogs. Bone marrows were obtained from eight dogs that had been chronically irradiated beginning at 21 days of gestation or after birth and eight age-matched controls. Of these irradiated dogs, four were either preleukemic or exhibited frank acute nonlymphocytic leukemia. The other four were clinically normal but demonstrated abnormalities in their marrow that could be attributed to radiation effects and/or other pathologic changes. Fibroblasts from six of the irradiated dogs were significantly more radioresistant than those of their controls. Five of these six dogs subsequently succumbed to hematopathologic disease, while the two irradiated dogs with normal fibroblasts remained clinically normal, suggesting that this observed radioresistance may be linked to the disease process.

A circannual rhythm in rubella antibody titers

Abstract Rubella antibody titers were assayed from 191 blood samples taken during seven years (1973–1979) from a human female who had contracted German measles in 1965. The antibody dilutions, transformed to integers, fit a first‐order harmonic function with an assumed period of 365 days. The levels about which the titers oscillated decreased from 1973 to 1975 and remained stable thereafter. Amplitudes averaged 31% on either side of the level of oscillation. At certain times of the years 1977–1979 at the trough of the rhythm the subject would have been considered to be lacking in immunity against rubella despite history to the contrary. This example of a long‐term, circannual rhythm in an immunologic assay supports previous suggestions that immunity cycles over the seasons.

Increased in vitro radioresistance of bone marrow fibroblastic progenitors (CFU-F) from patients with acute non-lymphocytic leukemia.

The proliferative potential following in vitro irradiation of bone marrow fibroblastic progenitors (CFU-F) derived from four patients with acute nonlymphocytic leukemia (ANLL) and seven nonleukemic subjects was compared. The CFU-F from the ANLL patients were significantly more radioresistant than the CFU-F from the nonleukemic subjects. The increased radioresistance in ANLL patients was evident in both the mean slope of the survival curve (control = -0.385, ANLL = -0.256) and in the Do values (control = 2.68 Gy, ANLL = 4.61 Gy). Thus CFU-F derived from ANLL patients differ from those derived from nonleukemics in both radioresistance and in granulopoietic effects as suggested from previous studies.

Photoperiod and cell mediated immunity of clinically normal dogs

Abstract Previously, the authors have reported seasonal variations in cell mediated immunity in the dog during the period July, 1977 ‐ October 1978 as measured by whole blood lectin‐induced lymphocyte transformation. Peak activity occurred in the summer, suggesting association with photoperiodicity. Here the authors report on immune response of dogs kept indoors ‐ under controlled physical environment ‐ with a natural (outdoor) photoperiod or under a 12:12 h (LD) regime, and a control group kept in outdoor kennels. Peak immune activity in 1979 occurred in the winter, in both indoor groups as well as the outdoor groups subject to natural photoperiod. Since the indoor dogs were kept at a constant temperature and humidity in clean (filtered) air, photoperiod, temperature, and particulate air contaminants probably are not associated with seasonal variations in immunity. The underlying cause for either the seasonal variations or the shift from peak activity in the summer of 1978 to winter of 1979 is unknown. D...