Jitka Kobilková

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.

Peritoneal Washing Cytology on Fluid Hysteroscopy and After Curettage in Women with Endometrial Carcinoma

OBJECTIVE To assess the influence of fluid hysteroscopy with target biopsy of the endometrium and the influence of added curettage on the results of peritoneal washing cytology (PWC) in endometrial carcinoma. STUDY DESIGN In 42 women at risk of endometrial carcinoma, we performed fluid hysteroscopy with target biopsy of the endometrium and curettage. Evaluation of PWC of the pouch of Douglas was performed three times during the procedure: prior to hysteroscopy, after fluid hysteroscopy with target biopsy and after curettage. RESULTS On cytologic slides from peritoneal washings in 11 patients with carcinoma of the endometrium, malignant endometrial cells were found after curettage in 72.7%. There was no statistically significant difference in PWC prior to hysteroscopy (two women, 20%) or after hysteroscopy with target biopsy (three women, 30%). There was a statistically significant difference (.05 level) in positive PWC after hysteroscopy with target biopsy (three women, 33.3%) and after curettage (eight women, 88.9%). CONCLUSION Slides from carcinoma of the endometrium in PWC do not deteriorate after hysteroscopy with target biopsy of the endometrium, but tumor cells will appear in the pouch of Douglas after curettage.

Sexual development and life of women with gonadal dysgenesis

The sexual development and behavior of 37 women suffering from the gonadal dysgenesis syndrome were investigated. It was found that their sexual development was significantly retarded compared with a control group of 50 fertile patients of the same age. This retardation was greater in a subgroup of 19 women with the Turner syndrome than in a subgroup of 18 women with pure gonadal dysgenesis. The levels of gonadotrophins LH and FSH, estradiol, progesterone and testosterone in blood were similar in these two subgroups. In two-thirds of the gonadal dysgenesis syndrome patients, the estradiol level was mostly at the low end of normal. The assessment of their sexual life using the Sexual Activity of Women (SAW) and Sexual Function of Women (SFW) questionnaires indicated a lower sexual desire, a reduced orgastic capacity, and a weaker sexual activity in the pathological group. However, 24 patients living in a permanent and stable partner relationship at the time of the examination, did not significantly differ from the control group in their responses to the SFW questionnaire. The patients with gonadal dysgenesis syndrome were surprisingly well adapted to their shortcomings. The occurrence and intensity of most neurotic symptoms assessed by the N5 Questionnaire were scored lower by the patients with gonadal dysgenesis syndrome than by the control group.

Dicentric Yp chromosome in a patient with the gonadal dysgenesis and gonadoblastoma

SummaryA patient with a short stature, gonadal dysgenesis, and bilateral gonadoblastoma had 3 cell lines in the blood and in the skin: 46,X,dic (Y) (pter→q12: :12→pter) as a major cell line 46,X,del (Y) (q 12), and 45,X. The intensively fluorescent distal part of the Yq was deleted in both the Y-dicentric and Yq—chromosome. Both parents had normal karyotypes.

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.

Sexual life of women with the Stein-Leventhal Syndrome

The course of sexual socialization of 50 women suffering from the Stein-Leventhal Syndrome (SLS), on which the wedge resection of the ovaries was carried out, as examined using the HTDW (heterosexual development of women) questionnaire, did not differ from that of 50 normal women of the same age. Sexual life of SLS patients was examined using an interview and the SAW (sexual activity of women), SFW (sexual function of women), and SAI (sexual arousability inventory) questionnaires. Comparison with the findings in the control group showed that the average score in all the three questionnaires was within normal limits for both groups; the differences between the groups were not statistically significant. Among 45 SLS patients who had sexual experience before the surgery, 42 stated that no pronounced changes occurred in their sexual lives after resection of the ovaries.The average value of testosterone in the whole group (0.52 ng/ml plasma) was within normal limits. The level of the male sexual hormone tended to be higher in the subgroup of 19 patients with low orgastic capacity than in the subgroup of 31 orgastic SLS patients. The differences in the average scores of neurotic symptoms in the N5 questionnaire between the SLS patients and the control group were not significant.On the basis of the above findings, it is concluded that SLS patients, after wedge resection of the ovaries, are not more sexually arousable, more active, or more orgastic than medically healthy women.

Fröhlich electromagnetic radiation from human leukocytes: Implications for leukocyte adherence inhibition test

The Fröhlich coherent vibrations may be a source of an electromagnetic field generated by living cells in the frequency range from 0.1 to 10 THz. The electromagnetic field may cause the time dependent orientation (i.e. rotation or rocking) of the polar molecules of the ambient liquid medium and may attract them. The attracted molecules move together with the cell and the friction coefficient of the cellular motion, therefore, may depend on the field. The cell-generated electromagnetic field may interact with the surface charge of various solid-state materials causing attractive forces. These interaction attractive forces may be significant in the process of the leukocyte adherence to the surfaces of various materials. The hypothesis presented in this paper assumes that the exposition of leukocytes from immune individuals to antigen causes changes of the Fröhlich coherent vibrations resulting in decrease of the leukocyte adherence observed in the leukocyte adherence inhibition test.

46,XX gonadal dysgenesis and ovarian hypoplasia

Summary30 patients with the 46,XX gonadal dysgenesis or with a severe primary ovarian hypoplasia are described. In 13 of them the gonadal histology and the patterns of the steroid biosynthesis in vitro are given. The gonads could be divided into three groups: A) “gonadal dysgenesis” without any follicular apparatus, B) “severe ovarian hypoplasy”, C) “hypoplastic sclerocystic ovaries”. Gradual transitions between all these groups and familial occurrence of both hypoplasia and sclerocystic ovaries suggest that certain cases of the ovarian hypoplasia represent a part of the broader spectrum of regressive ovarian condition, appearing as “pure gonadal dysgenesis” in its most severe form.Zusammenfassung30 Patientinnen mit einer Gonadendysgenesie oder einer schweren Ovarialdysplasie und Karyotyp 46,XX werden beschrieben. Bei 13 von ihnen werden Daten über Gonadenhistologie sowie Steroid-Biosynthese mitgeteilt. Die Gonaden wurden in drei Gruppen eingeteilt: A. “Gonadendysgenesie” ohne Follikelapparat; B. “schwere Ovarialdysplasie”; C. “hypoplastische, sklerocystische Ovarien”. Graduelle Übergänge zwischen diesen Formen sowie familiäres Vorkommen von Hypoplasie und sklerocystischen Ovarien legen den Gedanken nahe, daß gewisse Fälle von Ovarialhypoplasie einen Teil aus einem breiten Spektrum regressiver Ovarialveränderungen darstellen. Die “reine Gonadendysgenesie” erscheint dabei als die schwerste Form.

Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer

Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules’ ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.

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.