Moshe Shifrine

Hypothesis for the Mechanism of Elevated Serum Copper in Cancer Patients

Neoplastic growths seem to interfere with normal processes regulating the serum level of ceruloplasmin, a copper-containing oxidase, which accounts for 96% of serum copper. Normal catabolism of ceruloplasmin in the liver follows desialylation. However, in patients with tumors, ceruloplasmin may be resialylated at the tumor cell surface or in peripheral blood. Decreased catabolism due to resialylation of asialo-ceruloplasmin could account for the increased concentration of serum copper noted in patients with neoplasia.

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.

Effect of Hypocholesteremic Agents on Protozoa.

Summary The hypocholesteremic agents, triparanol and benzmalecene, inhibit the multiplication of the sterol-synthesizing phytoflagellates, Ochromonas danica, O. malhamensis, Euglena gracilis, and the non-sterol-synthesizing ciliate. Tetrahymena pyriformis. The inhibition of multiplication of the Ochromonas species may be prevented by cholesterol, ergosterol, farnesol, squalene, lauric acid, oleic acid, linoleic acid, and linolenic acid. Oleic acid and linolenic acid were most effective.

Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase.

Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates the lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 microgram catalase or 100 microgram SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p less than 0.05), catalase (p less than 0.001) and SOD + catalase (p less than 0.001) on lymphocyte division was significantly greater when given prior to X-irradiation. The lack of an oxygen effect and the inability of SOD and catalase to protect human lymphocytes from X-irradiation suggest that 2- and /or H2O2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis.

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.

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...

Cell-mediated immunity in the dog in relation to disease: a review.

Abstract Canine cell-mediated immunity and its in vitro testing is reviewed. Lymphocyte stimulation tests and the leukocyte migration inhibition test are discussed as corollaries of in vivo cell-mediated immunity. Cloning of progenitor populations, characterization of cell surface markers and DL-A typing for studies of canine immunity are also reviewed.

CANINE TRANSFER FACTOR

Publisher Summary This chapter describes the canine transfer factor (TF). Three dogs were used in the first set of experiments. The first TF donor dog, immunized with C. immitis in FCA, exhibited a typical positive delayed type hypersensitivity (DTH) to coccidioidin after skin testing 9 days post injection. TF prepared from 200 ml of blood obtained from this dog 1 day later was inoculated into a recipient dog, whose skin was tested with coccidiodin daily for 6 days. No skin reaction was observed and a blood sample then was taken for the LST. The results before and after TF injection indicate transfer of sensitivity to C. immitis but not to PPD. TF also increased response to PHA. Second donor dog was similarly immunized with C. immitis in FCA, but skin tests with coccidioidin exhibited only an equivocal DTH. TF was prepared 9 days post-immunization. The recipient of TF from the second dog exhibited a transient sensitivity to PPD but a sustained sensitivity to C. immitis, with a peak activity at 17 days. This dog also had an increased reactivity to PHA with a peak at 10 days and declining thereafter.