scispace - formally typeset
Search or ask a question

Showing papers in "Experimental pathology in 1982"


Journal ArticleDOI
TL;DR: The geroprotectors, which were shown to delay the realization of the genetic programme of aging and age pathology development, prolong lifespan and inhibit carcinogenesis more effectively than those influencing the initiatial stage of spontaneous carcinogenesis.
Abstract: The problem of an interrelation between carcinogenesis and aging is discussed from the point of view of the two-stage model of carcinogenesis. Data on the carcinogenic effect of subcutaneously administered benzo(a)pyrene (BP), intravaginally applied 7, 12-dimethylbenz(a)anthracene (DMBA), and intravenously injected N-nitrosomethylurea (NMU) to young and old animals are presented. Both the obtained results and data from available literature show the absence of a uniform effect of age on carcinogenesis. Age-associated dynamics of carcinogen-metabolizing enzyme activity, accuracy in DNA repair, and proliferative activity of target and non-target tissues have been discussed as the determinant factors for observed differences. Data on the growth rate of some transplantable tumors in young and old animals are also presented. As a rule, the above tumors grow more rapidly in old animals in comparison with young ones. The role of age-associated hormonal, metabolic, and immunological changes in tumor promotion is discussed. The similarity is stressed of a number of changes occurring at organism, tissue, and cellular levels of integration both during natural aging and carcinogenesis. Some results of study on effects of geroprotectors on spontaneous carcinogenesis are summarized. The geroprotectors, which were shown to delay the realization of the genetic programme of aging and age pathology development, prolong lifespan and inhibit carcinogenesis more effectively than those influencing the initiatial stage of spontaneous carcinogenesis. Finally, the integral scheme of events taking place in cell, tissue, and organism during carcinogenesis is presented.

196 citations



Journal ArticleDOI
TL;DR: In this article, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle.
Abstract: Summary In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm®, a synthetic dermatoplastic material. More fractions with potential agtion upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose hielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.

64 citations


Journal ArticleDOI
TL;DR: Evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor), which seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factors of fibro Blast growth.
Abstract: Summary Reported in this paper are studies by which evidence was produced to increased formation of granulation tissue in rats, aged two and six months, seven days after repeated localised administration of brain extract from cattle with FGF activity (fibroblast growth factor). Such increased formation of granulation tissue was attributable to the formation in the same granulation tissue of larger amounts of capillaries, which actually provided conditions for better blood supply. The above increase was associated with stimulation of the synthetic function of fibroblasts and myofibroblasts in the granulation tissue. Comprehensive morphometric tests, including differential counting, appeared to show that additional effects had to be assumed, in particular on macrophages and lymphocytes. Such increase in angiogenesis seemed to suggest that in the in vivo model studied FGF proved to be, first of all, a factor of angiogenesis rather than a factor of fibroblast growth. The above results, as obtained from rats which differed in age, exhibited a certain variation in response to FGF. This seems to underline the importance of age-dependent examination also in the context of pharmacological studies.

62 citations



Journal ArticleDOI
Wilma M. Frederiks1, J. James1, Bosch Ks1, M.J.B. Schröder1, Schuyt Hc1 
TL;DR: Ischemia in the left lateral and median lobe of the rat liver was provoked by means of a small clip, as applied in human microvascular surgery, and the extent of necrosis was estimated quantitatively via morphometric measurements of the relative surfaces of necrotic tissue in photomicrographs of gallocyanin-stained serial sections.
Abstract: Ischemia in the left lateral and median lobe of the rat liver was provoked by means of a small clip, as applied in human microvascular surgery. After various periods of ischemia (30, 40, 50, 60 and 90 min) the blood flow to these lobes was restored. Twenty-four hours after restoration, the extent of necrosis was estimated quantitatively via morphometric measurements of the relative surfaces of necrotic tissue in photomicrographs of gallocyanin-stained serial sections. After periods of ischemia longer than 40 min, the percentage of necrotic tissue increased linearly with the period of clamping. After 40 min of total ischemia the changes in hepatocytes are for the greater part reversible, whereas after 90 min the majority of the cells have passed the "point of no return" and will no more be able to maintain their integrity.

50 citations




Journal ArticleDOI
TL;DR: After thorough examination of cells in culture and in experimental tumors by light microscopic and electron microscopic methods that conclusion has been drawn that malignant fibrous histiocytoma can develop from fibrosarcoma.
Abstract: Summary An established fibrosarcoma cell line (RFS) derived from a cadmium induced fibrosarcoma of rat and RFS-cells in different subcultures produced tumors in nude mice and baby rats which showed characteristics of fibrosarcoma, malignant fibrous histiocytoma and completely undifferentiated sarcoma. After thorough examination of cells in culture and in experimental tumors by light microscopic and electron microscopic methods the conclusion has been drawn that malignant fibrous histiocytoma can develop from fibrosarcoma. By this the assumption that malignant fibrous histiocytomas derive from tissue histiocytes is questioned. After the discussion of the general unspecifity of the storiform growth pattern and the cytology of malignant fibrous histiocytomas the idea is presented that many defined malignant soft tissue tumors inclusively fibrosarcomas may pass a phase which should morphologically be diagnosed as malignant fibrous histiocytoma. Conceding the practical value of this diagnosis we emphasize that the concept of the entity „malignant fibrous histiocytoma” should be critically reevaluated because of the probable heterogeneity of this tumor group.

28 citations


Journal ArticleDOI
TL;DR: The volumetric densities of mitochondria, SER, peroxisomes, secondary lysosomes, and lipid droplets increased significantly in comparison with those of the 18 days old fetus, while RER, Golgi area, and primary lysoomes were rather constant.
Abstract: Quantitative and qualitative changes in liver tissues during prenatal development were studied by electron microscopy and morphometry. On the 15th day, 30% of fetal liver volume consisted of hepatocytes, and the extrahepatocytic spaces amounted to 63%. The hemopoietic cells occupied 93% of the extrahepatocytic spaces. Immature bile canaliculi were observed and amounted only to 0.14% of extrahepatocytic spaces. The hepatocytes were irregular in shape and possessed several large lipid droplets which amounted to 19% of the cytoplasm. Although the rough surfaced endoplasmic reticulum (RER) was well developed, the smooth surfaced endoplasmic reticulum (SER) was not yet differentiated. The typical peroxisomes with nucleoid and glycogen were not observed in the cytoplasm. On the 18th day the volumetric densities of hepatocytes and bile canaliculi were increased. The typical peroxisomes with nucleoid appeared in the cytoplasm. The accumulation of glycogen which amounted to 12% of the cytoplasmic volume had taken place, while the volume of lipid droplets decreased significantly. In glycogen areas the differentiation of SER began. At birth the histogenesis of the liver was well established. The hemopoietic cells decreased in number and were confined to perisinusoidal spaces. The volumes of biliary capillaries and sinusoids were comparable with these of young rats now. The volumetric density of hepatocytes increased and occupied about 74% of the liver. The volumetric densities of mitochondria, SER, peroxisomes, secondary lysosomes, and lipid droplets increased significantly in comparison with those of the 18 days old fetus, while RER, Golgi area, and primary lysosomes were rather constant. The volumetric density of glycogen decreased rapidly at birth.

24 citations


Journal ArticleDOI
TL;DR: It is concluded that the formation of a stable extravascular plasma clot with reduced susceptibility to fibrinolysis could be the most important precondition for the initiation of vascular responses, and that all materials, substances or biofactors capable of activating the clotting cascade should also have the capacity to induce angiogenic responses.
Abstract: Summary Millipore filters belong to number of solid materials which interact with the chorioallantoic membrane (CAM) and frequently initiate local edemas sometimes accompanied by vascular responses. We observed that such reactions can completely be prevented by coating Millipore filter pieces with hydrophilic polymers (e.g. polyvinylpyrrolidone dextran) or by hydrophobic substances as liquid paraffin and vaseline. Protease inhibitors (Contrikal®, epsilon-aminocaproic acid) did not prevent such reactions but increased the incidence of vascular responses. By assaying several blood components we found a relationship between the initiation of vascular responses in the CAM and the process of blood clotting. If small amounts (5 to 10µl) of citrated bovine or human plasma are dropped on the CAM angiogenic responses occur as good as regularly. They are also initiated if the plasmas are recalified and small fibrin fragments are placed on the CAM. Chicken plasma, however, regularly induced such responses only in combination with bovine serum or following application of (or treatment with) fibrinolysis inhibitors. We conclude that the formation of a stable extravascular plasma clot with reduced susceptibility to fibrinolysis could be the most important precondition for the initiation of vascular respanses, and hat all materials, substances or biofactors capable of activating the clotting cascade should also have the capacity to induce angiogenic responses.

Journal ArticleDOI
O. Löw1
TL;DR: In this paper, the polynomial regression curve for the comparison of epithelium and colloid data seems to be influenced by the interstitium values, since a further growing of the colloid percentages is connected with a decline of the epithelia percentages.
Abstract: Summary The colloid and epithelium percentages in the thyroid gland are characterized by a noticeable variability and a zonal heterogeneity; in the border region an enriching of the colloid component is observed and in the central part a higher epithelium concentration. Studies with different net point distances and measuring areas led to the following conclusions: provided that a sufficient number of points are attached, a distance of 250μm may be used for common tests; the prolongation of the measuring time for lower distances than 100μm is often not accompanied by an essentially better accuracy. Measuring areas should not be too small, even between fields of 20 mm2 differences of a few per cents may be observed in the same slide. The polynomial regression curve for the comparison of epithelium and colloid data seems to be influenced by the interstitium values: up to about 30% colloid an increase of the epithelium values is seen, since a further growing of the colloid percentages is connected with a decline of the epithelium percentages.



Journal ArticleDOI
TL;DR: The unlabelled antibody-enzyme method with the peroxid enzyme-antiperoxidase complex (PAP-complex) was used to demonstrate carcinoembryonic antigen (CEA) or CEA-like substances in paraffin-embedded specimens of tumour tissues with an anti-CEA-antiserum of a rabbit.
Abstract: Summary The unlabelled antibody-enzyme method with the peroxidase-antiperoxidase complex (PAP-complex) was used to demonstrate carcinoembryonic antigen (CEA) or CEA-like substances in paraffin-embedded specimens of tumour tissues with an anti-CEA-antiserum of a rabbit. The anti-CEA-antiserum used in this study exhibited a high anti-CEA-activity and a low activity to an impurity. The paraffin-embedded specimens of tumour tissues were investigated at serum dilutions of 1:16, 1: 64, and 1: 256. The sections of colorectal cancer showed the highest content of CEA. In 36 of 37 cases the tumour tissue reacted to the anti-CEA-antiserum up to a dilution of 1: 256. The stomach cancer tissues contained significantly lower CEA-levels than the colorectal cancer. The sarcomas, malignant melanomas, the tumour of testis, the prostatic cancers and basal cell carcinomas of the skin were found to contain none or very low CEA-content. In most specimens of these tumours the CEA was not demonstrable at a 1: 16 dilution of the primary antiserum.

Journal ArticleDOI
TL;DR: Prostacyclin in investigated dosage exerts a protective effect on hepatic mitochondria, damaged during acute experimental pancreatitis in dogs, and this effect is comparable to treated groups.
Abstract: Summary Acute pancreatitis affects the subcellular status of the liver both by enzymatic toxemia and by the impairment of the protective function exerted by a normal pancreas on the liver. The aim of this study was to investigate the effect of the cytoprotective agent prostacyclin (PGI2) on hepatic mitochondria during acute experimental pancreatitis (AEP) in dogs. AEP was induced by the injection of a bile and trypsin mixture into the pancreatic duct, and experiments were terminated after 12 hrs with the exception of dogs with AEP 24 hrs (N = 5). The hepatic mitochondria from the group with AEP 12 hrs without treatment (N = 5) showed a significant impairment of succinate oxidation in St. 3 (with ADP) to 20.1 nanoatoms O×min−1× mg−1 of mitochondrial protein in comparison to healthy dogs (N = 4) −37.6 units. The respiratory control ratio (RCR) in the former group was half as great as in the control group (1.56 and 3.13 respectively). The ADP: 0 ratio in this group was impossible to calculate. DNP-stimulated ATP-ase activity was lowered to 50.6 nM Pi min−1mg−1 of protein in comparison to the healthy animals (642.7 units). In dogs AEP 12 hrs treated with PGI2 in the dose of 20 ng/kg · min for 12 hrs (N = 5) and in the group additionally pretreated with PGI2 for 1 hr before AEP (N = 5), the respective values of succinate oxidation in St. 3 were 22.2 and 26.5 units; RCR with ADP 2.05 and 2.07; ADP: O ratio 1.10 and 1.19 (in healthy dogs ADP: O = 1.90). DNP-stimulated ATP-ase activity was also augmented in comparison with the untreated group, 94.0 and 125.6 units, respectively. In the group with AEP 12 hrs without treatment, the ultrastructural examination of the liver showed severely damaged, mitochondria with swelling, destruction of limiting membranes and cristae. In the group with AEP 24 hrs without treatment the functional and morphological picture of mitochondria was improved in comparison to AEP 12 hrs and was comparable to treated groups. Prostacyclin in investigated dosage exerts a protective effect on hepatic mitochondria, damaged during acute experimental pancreatitis in dogs.

Journal ArticleDOI
M. Hohenegger, R. Kramar, P. Om, M. Weissel1, R. Watschinger 
TL;DR: The investigations suggest that different mechanisms are responsible for the reduction of the metabolic rate in acidosis and uremia; on principle, normalization of the metabolism defect is possible.
Abstract: Summary 1. In acute HCl-induced acidosis and in acute uremia due to bilateral nephrectomy oxygen consumption is reduced by about 50%. 2. This is normalized by amphetamine treatment in the uremic state or prevented by triiodothyronine pretreatment in acidosis. 3. The lipolytic effects of both, triiodothyronine and amphetamine, are present under acidosis as well as under uremia. 4. The investigations suggest that different mechanisms are responsible for the reduction of the metabolic rate in acidosis and uremia; on principle, normalization of the metabolic defect is possible.

Journal ArticleDOI
TL;DR: The joint occurrence of dense intranuclear particles with typical core particles in cases of chronic B hepatitis show that they are not specific for non A, non B hepatitis.
Abstract: Summary Dense intranuclear particles, 30 to 40 nm diameter, could be identified in liver specimens from female patients, who immediately after delivery had been inoculated with sera contaminated with non A, non B hepatitis. The same particles were described previously by Kendrey et al. (1975) in a case of acute hepatitis without clinical or serological evidence for hepatitis A and B. The joint occurrence of dense intranuclear particles with typical core particles in cases of chronic B hepatitis show that they are not specific for non A, non B hepatitis. The observed structures are likely to be nonspecific responses of hepatocytic nuclei to different hepatitis viruses. The nature of relationship to the infectious agent remains to be elucidated. Tubular structures in the endoplasmic reticulum and other cytoplasmic inclusions which had been demonstrated in liver cells from chimpanzees inoculated with non A, non B hepatitis, did not occur in our material.

Journal ArticleDOI
G. Egger1
TL;DR: A biased β -adrenergic effect was produced either by blocking the α - adrenergic component of endogenous catecholamines using phentolamine or by application of isoproterenol, which led to a prolongation of the lymphocyte phase of the inflammatory process.
Abstract: Summary A biased β -adrenergic effect was produced either by blocking the α -adrenergic component of endogenous catecholamines using phentolamine or by application of isoproterenol. Both experimental conditions led to a prolongation of the lymphocyte phase of the inflammatory process. A β -bias also curbed the activity of a substance (or substances) inhibiting the ingress of lymphocytes into the site of inflammation (subcutaneously injected Sephadex) around the fourth and fifth day after the onset of inflammation. This lack in activity is evidently connected with the prolonged lymphocyte phase.

Journal ArticleDOI
TL;DR: Characteristic features of the smooth muscles cell migration and ghost body formation observed in vascular lesions induced by intravenous administration of Lipofundin-S were studied and compared to lesions seen in other models.
Abstract: Summary Characteristic features of the smooth muscle cell migration and ghost body formation observed in vascular lesions induced by intravenous administration of Lipofundin-S (Braun, Melsungen) were studied and compared to lesions seen in other models. Phenomena revealed can be explained by alterations of the cell environment. The cell, producing ghost body looses a part of the cytoplasm and complies with the new environment. Thus ghost bodies play an active part in maintaining the equilibrium between the cell and its environment.

Journal ArticleDOI
TL;DR: By using the chorioallantoic membrane model, it is observed that the pharmaceutical preparation Curantyl induces vascular responses almost regularly and this effect was found to be dependent on the high concentration of hydrogen ions in this preparation and could be prevented by increasing the pH value.
Abstract: Summary Dipyridamole, a potent inhibitor of the nucleoside transport into cells, has recently been reported to stimulate the proliferation of capillary endothelial cells in the heart and skeletal muscle of rats following long-term treatment. We tested this drug on cultured calf aortic endothelial cells and obtained no evidence that dipyridamole is able to stimulate directly the proliferation and migration of these cells. By using the chorioallantoic membrane model we observed that the pharmaceutical preparation Curantyl® induces vascular responses almost regularly. This effect, however, was found to be dependent on the high concentration of hydrogen ions in this preparation and could be prevented by increasing the p H value. A direct angiogenic effect of dipyridamole could not be demonstrated on the CAM.

Journal ArticleDOI
TL;DR: The immunopathologic and histopathologic similarities of the experimentally induced LSR in horses and ponies to that of the hoof-laminae lesion in naturally-occurring and/or carbohydrate induced laminitis may offer insight into the pathogenesis of this complex disease.
Abstract: The occurrence of the Local Shwartzman Reaction (LSR) in equine species has not previously been reported. The molecular mechanism appears identical to that reported for the rabbit and other species. The immunopathologic and histopathologic similarities of the experimentally induced LSR in horses and ponies to that of the hoof-laminae (an extension of the skin) lesion in naturally-occurring and/or carbohydrate induced laminitis may offer insight into the pathogenesis of this complex disease.

Journal ArticleDOI
TL;DR: A decrease of total collagen content was found in the skin and was produced by a decrease of neural salt-soluble and acid- Soluble collagen and a slight increase of insoluble collagen was observed in theskin, liver and lungs.
Abstract: Summary Collagen content was measured in the skin, liver, lungs, kidneys and heart muscle of rats irradiated with a single dose of gamma rays (500 R). A decrease of total collagen content was found in the skin and was produced by a decrease of neutral salt-soluble and acid-soluble collagen. A slight increase of insoluble collagen was observed in the skin, liver and lungs.

Journal ArticleDOI
TL;DR: The results show that the digest system cancer-associated lymphocyte reactivity to CEA can be abrogated by conventional anti-CEA sera, which finding indicates that there exist closely CEA-associated "tumour-specific" antigenicities.
Abstract: Summary By means of the macrophage electrophoretic mobility technique we could show lymphocytes of patients suffering from cancers of the digestive system to be sensitized to carcinoembryonic antigen (CEA). These findings conflict with the common view that CEA is not immunogenic in humans. The aim of the present study was to look as to whether conventional anti-CEA sera can neutralize the activity of a CEA preparation which is responsible for the human lymphocyte response. When 60 ng CEA were preincubated with highly diluted anti-CEA serum and the resulting immune complexes were thereafter co-precipitated by protein A-sepharose, positive lymphocyte responses could not longer be obtained. This effect was observed with 3 anti-CEA sera in 3 cancer patients (colon cancer, stomach cancer, teratocarcinoma), who's lymphocytes responded to CEA by lymphokine release. Normal serum had no neutralizing effect. The anti-CEA sera did not influence the activity of another tumour-relevant extract (teratocarcinoma-derived), to which cancer patients' lymphocytes reacted regardless of the tumour site. The lymphocytes from an oesophagus carcinoma patient, though reacting to the teratocarcinoma preparation, did not respond to CEA, thus, logically, all other tests with normal serum and anti-CEA sera were negative, too. The results show that the digest system cancer-associated lymphocyte reactivity to CEA can be abrogated by conventional anti-CEA sera, which finding indicates that there exist closely CEA-associated “tumour-specific” antigenicities.

Journal ArticleDOI
TL;DR: Treatment of mouse mammary tumor virus (MMTV) with reserpine in vitro or administration of Reserpine 30 min after MMTV inoculation abolishes the viral infectivity in mice.
Abstract: Summary Treatment of mouse mammary tumor virus (MMTV) with reserpine in vitro or administration of reserpine 30 min after MMTV inoculation abolishes the viral infectivity in mice.

Journal ArticleDOI
TL;DR: Changes of nineteen features of tumour cell nuclei in hypernephroma and three following late metastases were investigated by use of the automated image system and showed objectively an increased cellular dedifferentiation during metastases.
Abstract: Summary Changes of nineteen features of tumour cell nuclei in hypernephroma and three following late metastases were investigated by use of the automated image system. Histograms of nuclei features from primary tumours and metastases were compared. They showed objectively an increased cellular dedifferentiation during metastasis. Various aspects of the capability of automated morphometry for investigation of tumours are discussed.

Journal ArticleDOI
W. Storch1, H Riedel1, B. Trautmann1, J Justus1, D. Hiemann1 
TL;DR: Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.
Abstract: Summary Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 3, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type χ and λ ), α 1 -antitrypsin, α 1 -fetoprotein, α 1 - and α 2 -glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HB s Ag and HB c Ag. The inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.

Journal ArticleDOI
TL;DR: The present work deals with a disturbed elastin and collagen metabolism in experimental atherosclerosis and shows simultaneous participation of these compounds in pathogenesis of this disease.
Abstract: Summary Experimental atherosclerosis in rats was produced by feeding them atherogenic diet for ten months. Elastin and collagen content of the arterial wall as well as some aspects of the metabolism of these proteins were studied. A decrease of elastin content was accompanied by its enhanced susceptibility to enzymatic hydrolysis in vitro. An increase of soluble collagen fractions in tissue and a simultaneously enhanced level of collagen catabolites in serum and urine were found. The present work deals with a disturbed elastin and collagen metabolism in experimental atherosclerosis and shows simultaneous participation of these compounds in pathogenesis of this disease.

Journal ArticleDOI
TL;DR: The microscopically unaltered sections of the mucosa, prior to development of overt neoplastic changes carcinomas in situ, superficial cancers and small-size adenocarcinomas revealed a simplified structure of enterocyte population, as compared with normal epithelium.
Abstract: Summary A stage-by-stage study of disturbances in enterocyte proliferation in the ileum and descending colon in the course of tumour induction by treatment with 1,2-dimethylhydrazine was performed. Even at early stages, an expansion of the zone of epithelial cell proliferation in the crypts and migration of dividing cells as far as to the crypt mouth, which is a manifestation of enterocyte differentiation disturbances, were observed. Enterocytes of the crypts chiefly proliferated through a short cycle, the mean duration of which was slightly greater than in normal intestinal tissue. The reduced cell loss in the epithelium and resultant disturbances of its steady state led to the accumulation of great numbers of atypical cells in the superficial layers of the crypts and formation of carcinomas in situ in the descending colon. The microscopically unaltered sections of the mucosa, prior to development of overt neoplastic changes carcinomas in situ, superficial cancers and small-size adenocarcinomas revealed a simplified structure of enterocyte population, as compared with normal epithelium. As tumours progressed, the heterogeneity of its component cell subpopulations increased, and several subpopulations, differing in mean duration of the mitotic cycle, were formed. Pathologic mitoses made up a greater portion (50–60 per cent) of the dividing cells of the descending colon, as compared with ordinary 4 per cent at all stages of experimental tumour induction.

Journal ArticleDOI
TL;DR: A multi-step radioimmunological test system was applied to the characterization of carcinoembryonic antigen (CEA) preparations obtained by column chromatography including ion exchange procedure and proved useful for CEA estimations in crude tissue extracts.
Abstract: Summary A multi-step radioimmunological test system was applied to the characterization of carcinoembryonic antigen (CEA) preparations obtained by column chromatography including ion exchange procedure. CEA content? were estimated by means of a sequential inhibition radioimmunoassay using Protein A-bearing Staphylococci for coprecipitation. Data were expressed as “units CEA” and compared with results obtained from commercial CEA-RIA kits. In addition, attempts were made to evaluate the presence of normal cross-reacting antigens in CEA preparations by the application of an antiserum to perchloric acid extract from normal lung tissue. Data from these tests were expressed as “units NLA” (NLA stands for “normal cross-reacting lung antigen”). The factor “units CEA/units NLA” proved useful as an indication of the tumor specificity of those antigenic components measured in the inhibition assay. Moreover, radioimmunoprecipitation tests with subsequent SDS Polyacrylamide gel electrophoretic analysis were performed in order to get information on the molecular weight of the molecule(s) involved in the radioimmunological CEA determination procedure. The test system displayed 1) highly specific CEA reagibility in the standard inhibition assay, 2) test sensitivity of about 200 pg CEA (when related to the Hoffman/La Roche test) and 1 ng CEA (when related to CEA-IRE-SORIN), 3) low reagibility to normal cross-reacting antigens, also when compared to the commercial tests, 4) a molecular weight of about 200,000 daltons for the component(s) measured, and 5) evidence of inhomogeneity of the CEA batches investigated and those international references available. The latter might in part be attributed to so-called species-specific CEA-related determinants. The test system proved also useful for CEA estimations in crude tissue extracts.