Martina Nedbalová

Cell-Mediated Immunity in Cervical Cancer Evolution

Cell-mediated immunity (CMI) response to different antigens was examined in healthy women, in patients with cervical precancerous lesions, and in patients with cervical cancer. Cervical lesions were diagnosed by cytological (PAP) smears, from examination by colposcopy, and from “punch” biopsy material by histology. CMI response is related to specific processes in healthy and cancer cells. CMI was investigated by leukocyte adherence inhibition (LAI) assay using specific antigen (prepared from cervical carcinoma tissue) and non specific antigen (prepared from blood of mice infected by LDH—lactate dehydrogenase—virus). The CMI responses of healthy women and cancer patients to the antigens used are different: the majority of T lymphocytes display adherence and non adherence, respectively (but the CMI responses elicited by the antigens are not equal and small quantitative differences are observed). Regardless of the CIN (cervical intraepithelial neoplasia) grades, CMI responses correspond either to healthy women or to cervical carcinoma patients (at about similar ratio of cases in all the CIN groups). Effect of non specific antigen suggests that cervical carcinoma transformation may be connected with reduction of mitochondrial activity similar to processes in LDH virus infection.

EFFECTS OF SINUSOIDAL MAGNETIC FIELD ON ADHERENCE INHIBITION OF LEUKOCYTES

Response of leukocytes to exposure to an external magnetic field with frequency 50 Hz and sinusoidal waveform was investigated in vitro using the leukocyte adherence inhibition (LAI) assay developed as a measure of cell-mediated immunity. Leukocytes taken from healthy humans adhere, but their adherence decreases after 1 hr of exposure to the magnetic field with magnetic induction of 1 and 10 mT. The majority of leukocytes taken from cancer patients before any medical treatment do not adhere, and exposure to the magnetic field increases adherence. Correlation between the LAI assay results and the cell-mediated immunity suggests an effect of magnetic fields on leukocyte immune function in humans.

Biophysical Insights into Cancer Transformation and Treatment

Biological systems are hierarchically self-organized complex structures characterized by nonlinear interactions. Biochemical energy is transformed into work of physical forces required for various biological functions. We postulate that energy transduction depends on endogenous electrodynamic fields generated by microtubules. Microtubules and mitochondria colocalize in cells with microtubules providing tracks for mitochondrial movement. Besides energy transformation, mitochondria form a spatially distributed proton charge layer and a resultant strong static electric field, which causes water ordering in the surrounding cytosol. These effects create conditions for generation of coherent electrodynamic field. The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively, and shifted and rebuilt frequency spectra. Disturbed electrodynamic interaction forces between cancer and healthy cells may favor local invasion and metastasis. A therapeutic strategy of targeting dysfunctional mitochondria for restoration of their physiological functions makes it possible to switch on the natural apoptotic pathway blocked in cancer transformed cells. Experience with dichloroacetate in cancer treatment and reestablishment of the healthy state may help in the development of novel effective drugs aimed at the mitochondrial function.

Effects of Magnetic Field 0.1 and 0.05 mT on Leukocyte Adherence Inhibition

T lymphocytes taken from healthy humans and cancer patients before and after medical treatment were exposed to the magnetic field 0.1 and 0.05 mT to study response of the cell-mediated immunity. Leukocyte adherence, which is considered to correlate with the cell-mediated immunity, was measured using an in vitro technique—leukocyte adherence inhibition (LAI) assay. Exposure to the magnetic field increases adherence of T lymphocytes especially those from cancer patients before medical treatment. The effects of exposure to the magnetic field 0.1 and 0.05 mT are similar to those of greater magnetic fields in the range of 0.5 to 10 mT. The effects of the AC and DC magnetic fields 0.05 mT do not display large differences attributable to the magnetic field.

Effects of sinusoidal magnetic field on adherence inhibition of leucocytes: preliminary results

The leucocyte surface properties manifest the cell-mediated immunity. The response of the cell-mediated immunity to external magnetic field was examined by observing leucocyte adherence to solid state surfaces. In the presence of antigen, leucocytes taken from cancer patients exhibit decreased adherence in contrast with adherence of leucocytes from healthy humans. After 1 h exposure to a sinusoidal magnetic field of 50 Hz and of 1 mT or 10 mT, adherence of leucocytes taken from cancer patients is strongly increased. The 1 mT magnetic field has stronger effect than the 10 mT field.

Diseases caused by defects of energy level and loss of coherence in living cells.

Abstract Human and animal diseases are brought about by pathological alterations of production, composition, and conformation of macromolecules and structures in cells. Additional contributing factors include changes in physiological states caused by disturbances of energy supply, energy transduction, energy dissipation in moving or oscillating parts, and parasitic energy consumption. Disturbances of energy states may endanger existence of the system. The cell-mediated immunity (CMI) response of T lymphocytes correlating with their adherence properties was examined using antigen prepared from the serum of inbred laboratory mice strain C3H H2k infected with lactate dehydrogenase elevating (LDH) virus. LDH virus is a parasite on the cellular energy system. Significant CMI response was elicited in T lymphocytes prepared from the blood of patients with cancer of different phenotypes, acute myocardial infarctions, schizophrenia, and recurrent spontaneous abortions in early pregnancy from unknown reasons. The CMI response is assumed to monitor transferred information about decreased levels of energy states and decoherence in the cells caused by mitochondrial malfunction, parasitic consumption, production of lactate, and possibly other disturbances. The LDH virus infection or similar pathological processes caused by different agents might be connected with the diseases and monitored by the examined CMI response. A large amount of mitoses with chromosome defects in aborted fetuses suggest increased mutability of genomes caused by defective energy states.

Effects of Sinusoidal 0.5 mT Magnetic Field on Leukocyte Adherence Inhibition

Exposure of T lymphocytes to an external 50 Hz and 0.5 mT magnetic field was investigated in vitro using leukocyte adherence inhibition (LAI) assay which is a measure of cell-mediated immunity. Adherence of T lymphocytes taken from healthy humans and from cancer patients before and after medical treatment is enhanced after 1 h exposure to the magnetic field. The experimental findings for the magnetic field 0.5 mT are compared with published data for 1 and 10 mT. The results are consistent with suggestions of magnetic field effects on immune function in humans.

STUDY OF THE INTERACTION FORCES IN HUMAN CD4LY

Abstract The cluster formation of CD4Ly cells (a subpopulation of T lymphocytes) in suspension was examined. CD4Ly cells were prepared from blood taken from cancer patients and from healthy counterparts (blood donors). CD4Ly cells taken from cancer patients formed tightly bound clusters in suspension with corresponding tumour antigen or LDH (lactic dehydrogenase) virus antigen. Cluster formation was a rare event in suspensions with CD4Ly cells taken from healthy humans. Cluster formation coincides with decreased adherence of CD4Ly to solid state surfaces and suggests strong mutual interaction between CD4Ly. A tentative theoretical explanation based on the Frohlich coherent vibration hypothesis is given.

In vitro T lymphocyte adherence capabilities under the influence of lower induction values (0.1 – 0.01 mT) of 50 Hz external magnetic fields

Our research thus far has concerned the impact of external magnetic fields (50 Hz) and low (0.01-10 mT) induction on adherence capabilities of T lymphocytes obtained from the blood of patients with head and neck tumors. We know that the in vitro adherence capability of T lymphocytes towards surfaces in cancer patients is less than that of control. Previously, we have found that exposure to magnetic fields (50 Hz / 0.01-10 mT) increases the capability of T lymphocytes, in larynx/pharynx cancer patients, to adhere in vitro to surfaces, achieving almost physiological values, in not only pre-treatment patients but also those receiving treatment in the course of follow-up. The capability of T lymphocytes in controls (voluntary blood donors) to adhere to surfaces was also increased (50 Hz / 0.01-0.5 mT). The present study concentrates on the significance of the level of magnetic field induction in order to determine whether low induction values can restore T lymphocytes adherence capabilities. Testing a set of 20 patients showed a statistically significant difference (p < 0.05) in the in vitro adherence capacity of T lymphocytes between both 0.01 and 0.05, and 0.1 mT induction levels. In the control group (patients diagnosed with chronic sensorineural hearing loss) there was even a statistically significant difference between induction values of 0.05 and 0.01 mT. Therefore, we concluded that lower induction values resulted in a more biologically significant response.

The Comparison of Methods for Determination of Humoral and Cell-Mediated Immunity in Patients with Breast Cancer

We observed the immunological answer to antigens obtained from the human malignant breast tumor and from the blood of inbred mice strain C3H/H2K infected by LDH virus. We compared the modified ELISA method for humoral immunity with the leukocyte adherence inhibition (LAI) assay for cell-mediated immnunity. The modified ELISA method is suitable for early diagnosing and monitoring antibodies in a malignant breast tumor simultaneously with senological examinations which include mammography and clinical examinations, because the antibodies are determined in a high number of samples by single application.