Neuroepigenetics of stress.

Stress, a common if unpredictable life event, can have pronounced effects on physiology and behavior. Individuals show wide variation in stress susceptibility and resilience, which are only partially explained by variations in coding genes. Developmental programing of the hypothalamic-pituitary-adrenal stress axis provides part of the explanation for this variance. Epigenetic approaches have successfully helped fill the explanatory gaps between the influences of gene and environment on stress responsiveness, and differences in the sequelae of stress across individuals and generations. Stress and the stress axis interacts bi-directionally with epigenetic marks within the brain. It is now clear that exposure to stress, particularly in early life, has both acute and lasting effects on these marks. They in turn influence cognitive function and behavior, as well as the risk for suicide and psychiatric disorders across the lifespan and, in some cases, unto future generations.

The role of the T lymphocytic cell cycle and an autogenous lymphocytic factor in clinical medicine.

In this study 315 individuals (25 controls, 290 chemically sensitive immunocompromised patients) were investigated. Each patient had been on a standard therapy of avoidance of pollutants, nutritional supplementation, and injections of antigens for foods, and biological inhalants, but did not attain their immunological competence. Peripheral lymphocytes were collected and DNA histograms were constructed. The flow cytometer was used to evaluate the cell cycle, haematological, and other immunological profiles. From the other portion of the blood specimen, lymphocytes were propagated in vitro, harvested, and a lysate, termed the autogenous lymphocytic factor (ALF), was prepared. When treated with ALF, 88% of these individuals showed a significant (p < 0.001) clinical improvement which correlated with laboratory findings, involving regulation of abnormal cell cycles, increase in total lymphocytes and subsets T4, T8, (p < 0.05) and cell mediated immunity (CMI) response (p < 0.001). The ALF presumably acts as a biological response modifier. The cell cycle and ALF provide clinical tools for diagnosis and regulation of immunological incompetence.

Mitogenic effects of mycotoxins on T4 lymphocytes.

Mycotoxins have compromising effects on varied biological systems, even when ingested at levels which do not evoke manifestations of clinical mycotoxicoses. No data have been previously found as to the therapeutic and mitogenic effects of mycotoxins. This was the objective of the present work. Human peripheral T4 lymphocytes were obtained by venipuncture, propagated in RPMI 1640 medium and challenged with varied concentrations of aflatoxins, B1, B2, G1, and G2. The cells were stained with propidium iodide and fluorescent isothiocyanate (FITC) and examined microfluorometrically. All the mycotoxins were significantly mitogenic on the basis of dose response. No adverse effects were observed when doses of 10, 50 and 100 micrograms were administered on a modest clinical basis to volunteers.

Effects of haemolysins of groups A and B streptococci on cardiovascular system.

Anaesthetized New Zealand white rabbits and rats were either injected or infused with streptolysin S and group B streptococcal haemolysins in order to observe the haemodynamic actions of these haemolysins. Results showed that streptolysin S had little or no effect. In contrast, group B streptococcal haemolysin showed significant hypotensive action as manifested in rapid reduction of systolic, mean, diastolic and pulse pressures, and a limited number of deaths due to shock.

Kinetics of hemolysin production in bovine group B streptococci.

Thirteen strains of group B streptococci etiologically related to bovine infections were investigated in order to observe the effects of non-hemoglobin iron and glucose on growth and hemolysin production; and to determine the necessity to stabilize the hemolysin with a carrier-stabilizer agent. Ferric citrate was diluted to give final concentrations of 1-11 micrograms/ml, added to iron-reduced (by CaCl2 precipitation) brain heart infusion media, inoculated and incubated at 37 degrees C. Parallel experiments were carried out with glucose. A variety of agents was employed to act as hemolysin stabilizers. Hemolysin production was detected by lysis of sheep erythrocytes. Both iron and glucose were crucial in concentrations 5-7 micrograms/ml and 0.5-1% respectively. Bovine serum albumin-starch mixture acted as an excellent stabilizer.

Iron and glucose affecting growth and haemolysin production in human strains of group B streptococci.

Seven strains of group B streptococci aetiologically related to humans were investigated in order to observe the role of glucose and medium iron on their growth and haemolysin production, and the necessity of a 'carrier' molecule to ensure the stability of the haemolysin. Both growth and haemolysin production were significantly influenced by glucose and medium iron concentrations. Iron concentrations between 5 and 7 micrograms/ml and 0.5% to 1% glucose were critical. Maximum haemolysin production (detected by lysis of sheep erythrocytes) was obtained during the late exponential phase of the growth cycle, but declined, producing sigmoidal-like curves as the organism entered the stationary phase. RNA-core, serum and bovine serum albumin, stabilizers of streptolysin S had no stabilizing effect for the haemolysin of group B streptococci. However, bovine serum albumin-starch mixture (0.5% bovine serum albumin and 0.5% starch in phosphate buffered saline or brain-heart infusion) was an effective stabilizer.

The role of iron in the growth and hemolysin (Streptolysin S) production in Streptococcus pyogenes.

Four strains of Streptococcus pyogenes were propagated at 37 degrees C in a reduced iron medium supplemented with Fe3+-citrate to give concentrations of 1 through 11 micrograms per milliliter, in order to observe the effects of iron on growth and on the vitro production of Streptolysin S. Both growth and hemolysin production were observed to be influenced by medium iron concentration of which 1.2 micrograms per ml of iron was critical. Hemolysin was produced during the exponential phase of the growth cycle with maximum yield as the organism entered the stationary phase. Hemolytic activity (which was accepted as the ability of the hemolysin to lyse sheep erythrocytes) fell below detectable levels as the organisms entered fully into the stationary phase (9-10 hours post incubation). Serum (bovine, human, chicken) was observed to have a high stabilizing effect on the hemolysin.

Immunological response of chickens to eastern equine encephalomyelitis virus.

The dominant immunoglobulin against eastern equine encephalomyelitis (EEE) virus and its duration and the longevity of the EEE virus haemagglutination inhibition (HI) antibodies were determined in sentinel and 125 immunised and hyperimmunised domestic chickens by enzyme-linked immunosorbent assay and the HI test respectively. The chickens ranged in age from 10 weeks to 18 months, were of varied pedigrees and from different countries. Results show that the HI antibody (IgG) is short-lived. It peaks and disappears within 30 days. The secondary response is dominated by the IgM immunoglobulin which is relatively long-lasting. These results are contrary to classical expectations and were observed in all the chickens studied. If these observations are found to be characteristic of birds generally, the present standard method of EEE virus seroepidemiological surveillance must be modified to be effective.

Epidemiological investigation for arboviruses in Jamaica, West Indies.

Arbovirus investigation in Jamaica was undertaken between 1960 and 1975. Serological studies showed that antibodies to dengue type virus and St. Louis encephalitis virus (SLE) were prevalent throughout the island for several years. In urban communities, the incidence of dengue antibody was higher than for SLE; however, in children under 10 years of age antibody to both viruses was rarely present. In rural areas, SLE was prevalent in adults and children. This virus was isolated fom Culex nigripalpus (mosquitoes) and from a nestling Mockingbird, Mimus polyglottos, in the same rural area. Dengue type 3 and type 4 were isolated from the sera of patients in an urban area, during two epidemic periods, 1963 and 1968. No other group B arbovirus was encountered on the island. Group A arbovirus was virtually absent prior to the eastern equine encephalomyelitis outbreak of 1962. That virus was isolated from brain tissue of humans and equines. Two strains of Cache Valley virus from mosquitoes, Anopheles grabhami, one strain from Aedes taeniorhynchus, and a strain of Wad Medani virus from a tick, Amblyomma cajenense, were also isolated.

The role of chickens in the epidemiology of eastern equine encephalomyelitis virus in Jamaica.

Since 1962, when Jamaica experienced its first and only outbreak of eastern equine encephalomyelitis (EEE), surveillance for the causative virus has been in progress. Wild birds, rodents, mosquitoes, sandflies and sentinels (domestic chickens, guinea pigs, mice and hamsters) have been constantly examined for EEE virus and serological conversion. In essence, only negative results have been obtained. Since June 1976, domestic chickens have been investigated as a possible reservoir and several have been found to have haemagglutinating antibodies, with titres ranging from 1:10 to 1:160. These titres fell rapidly, eg, from 1:160 to 1:10 within 60 days. These results incriminate the domestic fowl as a major reservoir for the virus, and suggest that the life of immunoglobulins against EEE is short in birds. Thus, the large number of negative serological tests found in previous investigations might be misleading since positive sera might have been missed between intervals of capture and recapture of the birds. The results indicate that investigators could usefully modify their procedure by bleeding wild birds as early as one to two weeks after initial capture. The importance and duration of the dominant avian anti-EEE virus immunoglobulins should be investigated.