Search PubMed⌕ Search

Biomedical subjects

G Zajicek

Publications and source records attributed to G Zajicek.

At least 127 records · Page 7Linked to original sources
PubMed1981

On the relevant model for human cancer.

A conceptual structure for the relevancy assessment of cancer theories to clinical cancer is presented. The organism is stratified into hierarchies among which, the cell represents the lowest. Cells are aggregated into tissues and tissues, into organs. Organs are assembled into organ systems constituting the human organism. In each hierarchy an elementary unit, or holon is defined. Since structures in the organism are generally characterized by specific functions they perform, it is possible to define also hierarchies of functions and assess their importance quo ad vitam. This hierarchical classification serves here for the grouping of theories and observations in cancer. Genetic mutation or cell fusion for instance belong to the subcellular hierarchy. Observations made on single cells e.g. locomotion or adhesion, belong to the cell hierarchy. Tissue culture experiments are grouped into the tissue hierarchy, while carcinogen induced neoplasms are organ system hierarchy experiments. Medicine operates in the organismic hierarchy regarded herewith as the highest.

Cell Physiological Phenomena↗
PubMed1981

The risk of chemotherapy.

Human survival curves may be classified according to the magnitudes of their hazard rate derivatives into three elementary shapes or groups: Aging (lambda' (t) greater than 0), random death (lambda' (t) = 0) and regeneration (lambda' (t) less than 0). Each observed survival curve is assumed to be composed of one or more elementary shapes. The aging pattern is observed in population cohorts from the age of 15 years and onward. It underlies survival curves of experimental animal treated by whole body irradiation which is assumed to act via the nervous system inducing generalized hypoplasia by impeding its trophic function. The whole process is manifested by an increasing lambda (t). Regeneration, is associated with the mobilization of reserves to withstand a noxious perturbation. The regeneration pattern is observed in patients surviving myocardial infarction, or recovering from surgical intervention. It is shared also by all survival curves of the 4th report on end results of cancer, and is assumed to reflect the beneficial role of neoplasia. While the hazard rate lambda (t) reflects mortality, its derivative lambda' (t) is viewed here as a measure of morbidity, so that cancer treatment effectiveness has to be assessed by its influence on both. A beneficial treatment ought to reduce them and vice versa. Most survival curves published in the modern cancer literature indicate an increasing morbidity accompanying treatment manifested by a positive hazard rate derivative (lambda' (t) greater than 0).

Aging↗
PubMed1981

The classification of continuous replicator pathologies.

A framework for the classification of continuous replicator (CR) pathologies expressed by cell kinetic changes, is presented. Each CR (e.g. GI mucosa or epidermis) is characterized by an origin, a periphery and a trajectory (called tissue radius) along which cells are displaced. The state of a cell on the radius is defined by two coordinates. Its distance from tissue origin 'x' expressed in cell locations, and its cruising velocity v(x), proportional to the cell production among cells separating it from origin. S(x) = x integral of o v(t)dt, represents further the net cell production associated with cell displacement from origin up to location x. The cell is regarded as a point advancing in a rectlinear motion defined by two coordinates (x,S(x)), tracing an S(x) graph outlining the proliferation differentiation states of a CR system. The S(x) graph is treated as a geometrical figure and the comparison of different CR pathologies reduces to the formulation of congruence laws. Three CR pathological entities are outlined: 1) Hemolytic pathologies e.g. hemolytic anemia, psoriasis, celiac disease and cervical erosion. 2) Hyperplastic pathologies e.g. polycythemia, papilloma and adenomatous polyp and 3) Hypoplastic pathologies e.g. aplastic anemia, skin and endometrial atrophy. Each pathology is marked by a typical S(x) graph.

Cell Transformation, Neoplastic↗
PubMed1981

The histogenesis of glandular neoplasia.

Tissues in the organism may be divided according to their proliferative capacities into three categories: 1. Fast replicators (FR) e.g., epidermis; 2. Slow replicators (SR) e.g., liver and 3. Non replicators (NR) e.g., nerve cells. Evidence is presented that FR as well as SR tissues continuously proliferate exhibiting two distinct histomorphological structures; a progenitor region in which cells are formed and a functional region into which they enter. Throughout their displacement, the cells cover a typical path denominated as tissue radius. The SR tissues e.g., parotid gland, mammary gland, liver and prostate, exhibit similar ontogenies, and proceed during regeneration and neoplasia through similar stages. All are compound glands with two distinct stem cell types, one residing in the excretory duct epithelium and the second in the intercalated duct. Each stem cell gives rise to its typical neoplasm. Excretory duct originating neoplasms consist of papillomas, epidermal and adenocarcinomas, while intercalated stem cell bound neoplasms embrace the canalicular adenoma, oncocytoma acinic cell and lobular carcinomata. All tissues continuously stream along the tissue radius. Evidence is presented that even the liver cords are continuously displaced from the limiting lamina toward the terminal hepatic (or central) vein. The histological image of these tissues actually reflects an instantaneous picture of cells in a continuous flux.

Animals↗
PubMed1981

On the derivation of cell kinetics from histomorphology, observed in the rat incisor odontoblast.

A method to extract cell kinetic information from histomorphology is presented. Each replicating tissue is essentially an ordered structure with an origin where cells are formed and a periphery toward which they are displaced. The displacement path is called the tissue radius. The tissue variables may be studied in two domains, space and time. The first embraces all the states a cell may assume while the second specifies the cell transition rates. During steady state both domains are related linearly. These ideas are illustrated in the rat incisor odontoblast population whose life expectation is determined by the tooth wall shape. The odontoblast cell population paves the interior of the tooth wall delimiting a cone-shaped pulp. Near the root apex the dentine wall is barely visible. As one proceeds distally, the wall thickens while the pulp narrows. Pulp narrowing is associated with odontoblast cell loss whose magnitude may be deduced from the change of the pulp circumference CI(x) (x is the distance from tooth origin). The odontoblast force of mortality mu(x) may be calculated from the instantaneous perimeter change:mu(x) = - CI'(x)/CI(x); where CI'(x) stands for the derivative of CI(x). This equation serves for the construction of the odontoblast life table which may be studied in space and time.

Animals↗
PubMed1980

Neoplasia withstands cancer.

A theory is presented which regards cancer as a systemic disease caused by carcinogens. The organism protects itself by mobilizing its stem cell pool which proliferates in form of a neoplasm to withstand the deterioration of systemic cancer. These ideas are illustrated in form of a mathematical model which reproduces the known epidemiological functions such as: Age specific cancer incidence, prevalence, mortality and cancer survival. Their shap supports the theory and is consistent with the above assumptions. The model may be utilized further for the estimation of cancer prevalence and the degree of interaction between chronic systemic diseases and cancer. Since these features of the model are independent of the above assumptions, it may be applied to cancer epidemiology as such.

Age Factors↗
PubMed1980

The risk of cancer therapy.

Survival times of treated cancer patients are distributed lognormally. This density function exhibits a peak accompanied by a long tail which asymptotically approaches the abscissa. The lognormal conditional failure rate, known also as force of mortality, which describes the chances of a patient remaining alive, initially climbs, to decline at a later phase. This decline is observable in all survival curves of the "Fourth report on the end results of cancer" in the U.S., and has been documented also by other epidemiological surveys. It implies that with the progression of the disease the chances of the average patient to survive improve. This pattern indicates the existence of a mechanism which is assumed to be associated with neoplasia, and assists the patient to withstand cancer. The initial rise of the force of mortality is assumed here to be associated with cancer treatment which undermines the beneficial role of neoplasia.

Humans↗
PubMed1980

Who is afraid of carcinogens?

The reevaluation of previously reported studies in carcinogenesis indicates the existence of a mechanism which protects mice from the carcinogenic hazard, Mice had been subjected to ultraviolet radiation (U.V.), applied at regular doses and intervals (10). The time from the first application to the appearance of a 100 mm3 sized tumor was defined as "development time" td. The td times had been found to be distributed lognormally. Such a distribution indicates that the magnitude of td is proportional to the carcinogenic exposure which means that the longer a mouse is exposed to U.V. the slower the progression of its neoplasms. This may be evident also from the lognormal risk function or conditional failure rate lambda (td) which initially rises in these animals to a maximum, whereupon it declines. The declining risk function supports the existence of a protective mechanism in the body which withstands carcinogenesis.

Animals↗
PubMed1980

Feedback in cancer.

The theory presented regards cancer as a systemic disease initiated by carcinogens, and neoplasia as the organism's main defence against it. Carcinogens are assumed to destroy a vital substance "A" which is replenished by a second, "B", produced by neoplastic stem cells. Cancer progression is manifested by a gradual deterioration of the "A" producing machinery accompanied by a compensatory proliferation of neoplastic "B" producing stem cells whose size is therefore closely regulated so as to meet the organism's demands. Any stem cell pool reduction leading to a loss of "A" or "B" is followed by a proliferation of the remaining stem cells to replenish the loss. Such may be observed in chronic lymphoblastic leukemia maintaining a nearly constant elevated peripheral lymphoblast count. Following selective lymphoblast destruction the count is rapidly replenished to its pretreatment level. The same mechanism is assumed to explain the detrimental effect of some surgical interventions on cancer patients. Neoplastic progression is postulated to a obey a "stem cell conservation" principle which when violated is followed either by a stem cell replenishment or aggrevates the patient's conditions. This conservation law introduces a new definition of carcinogenesis: Any process reducing the "A" or "B" producing machinery is regarded as a carcinogen. A definition embracing, surgical extirpation of normal or neoplastic stem cells or cell destruction by irradiation, chemotherapy or chemical carcinogens.

Carcinogens↗
PubMed1980

Computer image analysis of the optic disc.

A computer method for image analysis of the optic disc is presented. Black and white photographic transparencies of the optic disc were scanned by a scanning television camera. The image was digitized into not more than 4,000 x 4,000 points, each representing a value ranging between 0 and 255 gray levels. The images are depicted in two ways; either in the form of a topographic map (contour) in which the curves join points of identical light intensity, or as a relief that expresses the light intensity of every scanned line. This method emphasizes the qualitative parameters of the disc, and enables a quantitative determination of some disc pathologies.

Computers↗
PubMed1979

Computer image analysis of kidney histopathological sections.

Human renal histological sections have been photographed on a black and white transparency and digitized. The digitizing camera, an image dissector, converts a 2 cm2 picture into 400 x 400 numbers each representing the grey level value of sampled point. The grey levels are represented in the computer by number ranging between 0-255. In this scale 'O' stands for black and 255, for white. The program provides 2 grey level thresholds, which outline a window through which the picture is scanned. Only structures, whose grey level value lies in the window range, are taken into consideration. The thresholds are set during digitization from the console switches. Image analysis is performed on-line in real time.

Color↗
PubMed1979

Metastasis as a beneficial process.

The most important message to be found in the "Fourth report on end results in cancer" in the U.S., states that with the progression of cancer, its force of mortality declines. This has been reexamined in the present study. The declining force of mortality implies that as the disease advances the chances of the average patient to survive, improve. Since in the cancer patient all vital functions gradually deteriorate, and the only process gaining with time is his tumor load, one has to consider the possibility that the improving chances of the cancer patient could be linked with the amount of tumor mass in his body. These ideas are illustrated by the following example. Cancer could result from a gradual loss of a vital tissue product 'A', to be replaced by an analogous tissue product 'B' which is of embryonal origin. In the adult, 'B' is produced by stem cells which gradually adapt to the loss of the primary product and increase in number. 'B' is less efficient than 'A' to meet the necessary vital functions. Its deficiency in quality is however augmented by quantity. In order to keep up with the increasing demand, the stem cells proliferate and spread throughout the organism where each metastasis continues to secrete 'B'. The penalty inflicted by this compensatory mechanism is relatively high. Some metastases hit vital functions, and the increasing tumor load depletes the available energy sources. The net effect however is beneficial since without metastasis the organism would have succumbed to the disease in its earliest stage.

Adaptation, Physiological↗
PubMed1979

Proliferon: the functional unit of rapidly proliferating organs.

Continuously replicating organs are generally composed of several cell population types. These may be divided according to their function into two classes: 1. parenchyma: cells destined to perform a certain metabolic function peculiar to the organ under study, 2. supporting cell populations, consisting of fibroblasts and vascular supply always accompanied by nerve fibers. The kinetics of all the cells are highly coordinated. They all share one progenitor region. It is postulated that in this common progenitor region the two cell population classes are assembled into complex units denominated as proliferons. The proliferon starts its existence as a whole, matures as a whole and disintegrates at the organ periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibers. This model has been previously called upon to describe the kinetics of the rodent incisor tooth and the intestinal mucosa. It is assumed to be the elementary functional unit of all rapidly proliferating organs such as: skin, hair, endometrium, bone marrow, intestinal mucosa and rodent incisor.

Adult↗
PubMed1979

A new method for the estimation of cell cycle phases.

A method is described, which is applicable to cell renewal systems with an anatomical structure in which all cell locations may be uniquely mapped. Its use is demonstrated on the rat incisor inner enamel epithelium, which forms a one cell thick column in the sagittally sectioned tooth. Cells born in the apical part of the column migrate toward the distal end of the tooth, where they mature. As the cells migrate along the column, they traverse the various cell cycle phases. The present study has been designed to estimate the probability of a cell being in a given phase; all cells touching the basement membrane were numbered, and the number of cells separating any two cells was taken as a measure of distance. Since generally all cells move in one direction (lateral cell migration may occur), it is possible to solve the problem with the aid of functions describing the renewal counting stochastic process in which cell distance serves as an independent variable. The method predicts labelled cell and mitotic rates which agree with those estimated in the usual way. It was then utilized to estimate the fraction of cells in G2.

Animals↗
PubMed1979

On the progenitor cell migration velocity.

An attempt is presented to extract cell kinetic information from histomorphological features. It is applicable to rapidly proliferating tissues like the intestinal epithelium. Each replicating tissue has an origin where cells are formed and a periphery toward which cells migrate. The migration path along which they move is denominated as tissue radius on which all cell positions are mapped. Cell migration on the radius is associated with cell proliferation at tissue origin. Each mitosis there is associated with the displacement of all cells distal to it by one cell position. The more mitoses positioned between a cell and tissue origin, the greater its migration velocity. It is possible therefore to derive the cell migration velocity v(x) from the cumulative mitotic distribution on the radius, N(x). v(x) = N(x)/tm (tm = mitotic time). In this form v(x) represents also cell production at any point on the radius and may serve for the computation of other cell kinetic parameters like generation time. These arguments are illustrated on the rat incisor tooth inner enamel epithelium which has been studied in the normal and rapidly erupting tooth.

Ameloblasts↗