Optimization of the therapy of atopic dermatitis by means of immunotherapy

Taking into account disturbances in the functioning of the immune system in atopic dermatitis (AD) and the potentiating role of staphylococcal and other infections, the possibility of the optimization of the therapy of AD with the use of preparations having immunomodulating action and immunogenic activity is proposed. In the complex therapy of AD in children we used polycomponent vaccine Immunovac B-4, introduced intranasally and orally. Under the influence of immunotherapy the clinical characteristics of the patients had pronounced positive dynamics. A considerable decrease in the spread of the process, the degree of its severity and subjective symptoms was noted shortly after the course of vaccine treatment. Simultaneously the SCORAD index dropped from 64.5 to 39.4. During the later period of observation further decrease in the severity of the course of AD in children occurred, and the minimal characteristics were observed in 6 months of observation. At that time the SCORAD index fell to 19.9 +/- 1.34. The volume of pharmacotherapy and the number of acute respiratory infections considerably decreased, the positive dynamics of the quantitative and qualitative composition of the intestinal microflora was noted. The prolonged immunotherapeutic effect of the polycomponent vaccine made it possible to recommend the vaccine for the optimization of the therapy of AD.     

Influence of temperature fluctuations on Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium in cow manure

The effects of four average temperatures (7, 16, 23 and 33 degrees C) and daily oscillations with three amplitudes (0, +/-4, +/-7 degrees C) on the survival of the enteropathogens Escherichia coli O157:H7 and Salmonella serovar Typhimurium were investigated in small microcosms. Manure was inoculated with a green fluorescent protein transformed strain of either pathogen at 10(7) cells g(-1) dry weight. Samples were collected immediately after inoculation, and 1 and 2 weeks after inoculation for E. coli O157:H7, and immediately and after 2 and 3 weeks for Salmonella serovar Typhimurium. Population densities were determined by dilution plating and direct counting. In addition, total bacterial CFUs were determined. Growth and survival data were fitted to a modified logistic model. Analysis of the estimated parameter values showed that E. coli O157:H7 survived for shorter periods of time and was more sensitive to competition by the native microbial community than Salmonella serovar Typhimurium. Survival of both pathogens significantly declined with increasing mean temperatures and with increasing amplitude in daily temperature oscillations. The results indicated that responses of enteropathogens to fluctuating temperatures cannot be deduced from temperature relationships determined under constant temperatures.     

Two Modes of Cell Death Caused by Exposure to Nanosecond Pulsed Electric Field

High-amplitude electric pulses of nanosecond duration, also known as nanosecond pulsed electric field (nsPEF), are a novel modality with promising applications for cell stimulation and tissue ablation. However, key mechanisms responsible for the cytotoxicity of nsPEF have not been established. We show that the principal cause of cell death induced by 60- or 300-ns pulses in U937 cells is the loss of the plasma membrane integrity (“nanoelectroporation”), leading to water uptake, cell swelling, and eventual membrane rupture. Most of this early necrotic death occurs within 1–2 hr after nsPEF exposure. The uptake of water is driven by the presence of pore-impermeable solutes inside the cell, and can be counterbalanced by the presence of a pore-impermeable solute such as sucrose in the medium. Sucrose blocks swelling and prevents the early necrotic death; however the long-term cell survival (24 and 48 hr) does not significantly change. Cells protected with sucrose demonstrate higher incidence of the delayed death (6–24 hr post nsPEF). These cells are more often positive for the uptake of an early apoptotic marker dye YO-PRO-1 while remaining impermeable to propidium iodide. Instead of swelling, these cells often develop apoptotic fragmentation of the cytoplasm. Caspase 3/7 activity increases already in 1 hr after nsPEF and poly-ADP ribose polymerase (PARP) cleavage is detected in 2 hr. Staurosporin-treated positive control cells develop these apoptotic signs only in 3 and 4 hr, respectively. We conclude that nsPEF exposure triggers both necrotic and apoptotic pathways. The early necrotic death prevails under standard cell culture conditions, but cells rescued from the necrosis nonetheless die later on by apoptosis. The balance between the two modes of cell death can be controlled by enabling or blocking cell swelling.     

Nuclear antigens detectable with human autoantibodies

Sera of patients with rheumatic diseases often contain autoantibodies to nuclear antigens. Problems of the specificity of autoantibodies and of their usage for studying nuclear components and of the whole nuclear organization are reviewed.     

The identification of kinetochore proteins by using the sera of patients with collagenoses

Sera of rheumatology patients with antikinetochore autoantibodies are identified. Immunoblot of human cell proteins showed that all the sera contained autoantibodies to kinetochore proteins A and B. In Chinese hamster cells proteins with m. m. 45 kD, 100 kD and 110 kD are presumably kinetochore proteins, whereas in murine cells these are proteins with m. m. 45 kD 85 kD and 100 kD.     

Serum antibodies to brain protein antigens in cerebral palsy in children]

Using special brain antigen test-system ELITEST-24, ELISA assays of the serum of children with cerebral palsy were conducted. The data obtained were compared to relevant characteristics of the sera from neurologically and somatically healthy persons and patients with diagnoses of multiple sclerosis, schizophrenia, epilepsy and hepato-cerebral dystrophy according to special PC program VIZUAL and DIAGNOST. High specificity of the cerebral palsy anti-brain antigens reactivity was revealed by ELITEST technique. Moreover, the comparison of the mother-child pair immunoreactivity has been conducted. Evidence for hypothesis of epigenetically performing of children antibodies repertoires by mother-during-pregnancy immune status were obtained. Possible immunopathologic mechanisms of the disease are discussed.     

Role of virus-induced autoreactive T-lymphocytes, T-suppressors and the serum factor regulating their activity in the pathogenesis of experimental infection caused by the Langat virus in mice

The precursors of autoreactive T-lymphocytes (PARTL) have been detected in the spleen of mice infected with Langat virus. When introduced into syngeneic recipients, PARTL differentiate in their lymph nodes into autoreactive T-lymphocytes (ARTL) causing a fatal autoimmune disease in the syngeneic recipients in vivo and capable of destroying syngeneic cell cultures in vitro. In the thymus of mice infected with Langat virus T-suppressors (TS) inhibiting the differentiation of PARTL into ARTL have been detected. The serum of intact mice has been shown to contain the serum blocking factor (SBF) which suppresses the differentiation of PARTL and the activity of TS from donors having common H-2 haplotypes of the gene complex with serum donors. In the course of viral infection the decrease of SBF activity and, simultaneously, the activation of PARTL and TS occur. The activation of PARTL and TS in infected mice may be suppressed by the injection of the serum of intact donors identical in H-2 haplotypes. The injection of ARTL induced by Langat virus into syngeneic recipients infected with this virus provokes the transformation of asymptomatic infection into acute infection, while TS and SBF blocking the differentiation of PARTL protect the animals from death.     

Microelectrode recording of responses in visually observed neurons of the cat motor cortex

With a contact optical system it is possible to carry out intravital studies of neurons and other structures, stained with vital dyes in reflected light in a specially prepared specimen of the cat cerebral cortex. The high-quality characteristics of the optical system used have made combined morphological and intracellular electrophysiological investigations of these neurons possible. The nature of intravital morphological changes in cortical neurons was established in response to their puncture by microelectrodes with tips with different external diameters and configurations; certain morpho-functional correlations were found in the response of pyramidal neurons to disturbance of their temperature regime.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 8, No. 2, pp. 122–125, March–April, 1976.