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Biomedical subjects

D Komitowski

Publications and source records attributed to D Komitowski.

At least 55 records · Page 3Linked to original sources

Spontaneous in vitro malignant transformation in a xeroderma pigmentosum fibroblast line.

This paper deals with a spontaneous malignant transformation in one of our XP fibroblast lines. This cell line, designated XP29MA, was derived from a 14-year-old boy who did not show skin tumors or precancerous alterations either at the time of clinical examination or when the biopsy was taken. We have compared the following features in both the malignant and the benign cell line from which the malignant line developed: tumor formation in nude mice, repair capacity, cytogenetic status, light and electron microscopic characteristics. The benign cell line XP29MA had a doubling time of 4.3 d, did not form tumors in nude mice, showed a very low repair capacity (as determined by colony-forming ability, unscheduled DNA synthesis and alkaline elution) but exhibited a normal cytogenetic and ultrastructural status. In contrast, the transformed cell line XP29MAmal grew three times faster, formed colonies in methyl cellulose, gave rise to fibrosarcomas in nude mice, showed a drastically higher repair capacity, and was characterized by an extreme genetic imbalance, resulting from numerical and structural chromosome alterations of Nos. 1, 3, 4, 8, 12, 16, 17, 18, 20 and 21. Ultrastructural examination revealed fusiform and polygonal cells, the latter exhibiting large indented nuclei, vesicular dilatations of the endoplasmatic reticulum and numerous lysosomes. The higher repair capacity in XP29MAmal cells is tentatively explained in terms of reversion, enhancement of post-replication repair and/or expression of SOS-type functions.

Adolescent↗

Light and scanning electron microscopic study of testosterone-restored penile papillae in castrated rats.

Structural changes in various penile tissue from rats with differing circulating androgen levels were analyzed with light and scanning electron microscopy. Adult males were castrated and daily injected for 6 weeks with one of four physiologic amounts of testosterone propionate (TP). Results indicated that epithelium, subepithelial connective tissue, and the papillae protruding from the surface of the glans penis responded, more or less, in a dose-dependent fashion to the steroid. The least androgen-sensitive penile tissue was the epidermal stratum corneum, more sensitive was the maligiphian layer, and more sensitive still was the subepithelium. The penile papillae and their follicles were the most androgen-sensitive tissue. Specifically, the high testosterone, 400 micrograms and 800 micrograms TP, males experienced papillae that were thicker, taller, more densely arranged, and more highly keratinized than the lower testosterone, 100 micrograms and 200 micrograms TP, males. The function of the papillae may be to provide the female with the mechanical stimulation necessary to ensure a proper hormonal milieu for successful impregnation.

Animals↗

Segmentation of cell nuclei in tissue section analysis.

Image segmentation is a critical step in digital picture analysis, especially for that of tissue sections. As the morphology of the cell nuclei provides important biological information, their segmentation is of particular interest. The known segmentation methods are not adequate for segmenting cell nuclei of tissue sections; the reason for this lies in the optical properties of their images. We have developed new gradient methods of segmentation of previously presegmented images by taking these properties into account and by using the approximately circular shape of the cell nuclei as a priori information. In our first technique, the segment method, the images of the nuclei are divided into eight segments, special gradient filters being defined for each segment. This has enabled us to improve the gradient image. After searching for local maxima, the contours of nuclei can be found. In the second method, the method of transformation into the polar coordinate system (PCS), the a priori information serves to define a circular direction field for gradient computation and contour finding. In contrast with the first method, which offers a rapid, general idea about the nuclear shape, the PCS method permits precise segmentation and morphological analysis of the cell nuclei.

Animals↗

Reproductive physiology and penile papillae morphology of rats after sexual experience.

Research which examined acute and chronic changes in the reproductive physiology and morphology of male rats after mating is reported. A group of sexually experienced (SE) and a group of sexually inexperienced (SI) animals were castrated on day 110 of age. Those animals and a group of SE and a group of SI gonadally intact males were left undisturbed for 30 days, and all animals were killed on day 140 of age. Testes, epididymides, penes and levator ani muscles were heavier in SE males, and those males had increased titres of circulating testosterone. Moreover, testicular sperm production was higher in SE than SI males immediately after the weekly copulatory sessions. Scanning electron microscopic examination of the surfaces of the glans penes revealed that sexual experience slowed the decay of penile papillae. More importantly, SE-intact males possessed uniformly large penile papillae, while the large papillae on penes from SI-intact males were interspersed with smaller papillae in various stages of development. The results suggest that mating provokes substantial changes in the endocrine integrity, fecundity and penile morphology of male rats.

Animals↗

Characterization of BSp73, a spontaneous rat tumor and its in vivo selected variants showing different metastasizing capacities.

BSp73 arose spontaneously (1979) as intraperitoneal nodules together with ascites. Histologically, the nodules were classified as adenocarcinoma of the pancreas. During serial transplantation of ascites cells to a subcutaneous site, two variants appeared--one fast-growing, nonmetastasizing, the other slowly growing and metastasizing via the lymphatic system to the lung. From the in vivo selected variants as well as from the parental tumor, two types of tissue cultured cell lines were established. These differed in morphology, adherence to plastic, susceptibility to detachment by trypsin, and, above all, in the ability to metastasize upon reinjection into syngeneic recipients. From differences in growth kinetics in vivo it has to be concluded that variant cell types coexisted in the parental tumor in the form of precursors, which adopted their characteristic features (irreversibly) after a shift in the environment.

Animals↗

Digital picture analysis for studying the development of experimentally induced osteosarcoma.

We used the method of digital picture analysis to make a quantitative characterization, of stages of development of experimental osteosarcomas in rabbits. DMBA in gelatine pellets placed intraosteally served as a carcinogen to induce bone sarcomas. Of 25 animals treated, eight developed osteosarcomas classified as either osteoblastic, fibroblastic, or chondroblastic. We studied the process of bone neoplasia using radiographic, scintigraphic, and histological methods. To define the progress of neoplastic growth in each tumor we processed sequential radiographs of them by digital picture analysis. For this purpose, we developed a method for quantifying radiological changes using parameters independent of the rotation of the bone. In defining the histologic type of bone sarcomas, besides microscopic features we relied on quantitative criteria such as ratios of the newly formed bone and cartilage to the sarcomatous stroma. Our results, presented in this paper, indicate that digital picture analysis may be useful in characterizing experimental osteosarcomas as a model for therapeutic studies.

9,10-Dimethyl-1,2-benzanthracene↗

Epidermal-dermal junction during experimental skin carcinogenesis and cocarcinogenesis as revealed by scanning electron microscopy.

During epidermal carcinogenesis important changes in the epidermal-dermal junction take place. Because of methodological difficulties may be these changes, especially those concerned with three-dimensional organization of the junction, remain unsatisfactorily investigated. To obtain new information, we studied with scanning electron microscopy (SEM) the development of carcinogenic changes in the epidermis of mice induced by DMBA-TPA, DMBA alone, and by the cocarcinogen TPA alone. We correlated the results with those from transmission electron microscopy and light microscopy. Although the epidermal changes morphologically showed similarities, biologically they differed. With them, distinct changes in the epidermal-dermal junction developed, that could be followed through early, hyperplastic and neoplastic phases. With the SEM the first changes were seen in the basal layer of the epidermis and concerned the cell arrangement. SEM provided information about the localization and development of incipient epidermal carcinomas induced by DMBA-TPA and DMBA treatment, as well as about the changes in the basal lamina. These can be classified by their surface, their extent and their frequency throughout large regions. Our studies indicate that these changes vary greatly, depending upon the treatment used and the time of their development. Only the progressive disintegration of the basal lamina is characteristic of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

Rat mammary tumor classification: notes on comparative aspects.

Mammary tumors (170 spontaneous and 1,613 induced with 7,12-dimethylbenz[a]anthracene) in inbred SD rats were classified histologically. The neoplasms were divided into three main categories: fibroepithelial, epithelial, and connective tissue. In the fibroepithelial category, compound tumors showing a wide range of histologic structures with variation in the arrangement of both epithelial and connective tissue elements that differ among lobules occurred in 44 (25.9%) spontaneous and 1,027 (63.7%) induced neoplasms, whereas fibroadenomas occurred in 41 (24.1%) untreated and 175 (10.9%) treated rats. Uncommon fissured tumors were found in 1 (0.7%) untreated and 6 (0.4%) treated animals, whereas carcinosarcomas were found in only 10 untreated animals. In the epithelial category, tubular adenomas occurred in 48 (28.2%) untreated and 164 (10.2%) treated animals. Cystadenomas, duct papillomas, intraductal carcinomas, and anaplastic carcinomas were found less frequently. Adenoacanthomas occurred in only 12 (0.8%) of the treated animals. Among tumors with a fibrous component only, fibromas occurred in 22 (13%) untreated and 97 (6.0%) treated animals, Fibrosarcomas were less frequent, occurring in 4 untreated (2.4%) and 54 (3.4%) treated animals.

Adenocarcinoma↗

Intraglomerular microcirculation: measurements of single glomerular loop flow in rats.

With the use of a new fluorescent microscopic technique, we were able to measure the mean intracapillary velocities and pressures of single capillary loops of renal glomeruli of living rats. The technique involved photographing and recording the flow of fluorescent latex particles through the glomerular loops with a television monitor. In 25 rats the single glomerular loop flow velocity was 781 +/- (SD) 271 micrometers . sec-1. The mean diameter of the capillary loops measured 8.4 +/- 1.4 micrometers; their lengths were 72.3 +/- 37.5 micrometers. From the decrease in velocity of flow along the capillary loop, we were able to evaluate the filtration equivalent for the capillary surface. It was possible to measure intracapillary pressures of single glomerular loops continuously under microscopic control. High intracapillary pressures correlated with high intracapillary velocities. From the data we obtained, we were unable to calculate a filtration equilibrium at the ends of the observed capillary loops. For further correlations, we injected the glomeruli we had studied in the living state and examined them with the scanning electron microscope.

Animals↗

Experimental bone tumors as models of human bone tumors.

Experimental models of human bone tumors may be classified as causal, descriptive, and selective models. These models are useful for analyzing the morphology, biology, and therapy of human bone tumors. The application of these models, however, requires us to define clearly the questions to be answered and to consider the special features of experimental and human bone tumors. The suitability of experimental bone tumors as models can be determined only on the basis of a large amount of relevant experimental and clinical data.

Animals↗

Experimental infection of Tupaia belangeri (tree shrews) with herpes simplex virus types 1 and 2.

The susceptibility of Tupaia belangeri (tree shrews, which are primitive prosimian primates) to infection with herpes simplex virus (HSV) and the pathogenesis of HSV in these animals were investigated. Juvenile (28--45 days old) and adult (150 days old) animals were inoculated intravenously, intraperitoneally, or subcutaneously with HSV type 1 or 2 (25--10(5) plaque-forming units per animal). Clinical illness usually appeared in juvenile animals on the second day after inoculation, and the animals died between two and 14 days after inoculation. High titers of infectious HSV were recovered from liver and spleen. The histopathologic examination always showed severe liver changes with numerous necrotic areas. The morphologic events in the liver were designated as herpetic hepatitis. The next most common morphologic findings were encephalitis and fibrosis in the spleen. These results demonstrate the high pathogenicity of HSV types 1 and 2 in juvenile T. belangeri. In contrast, adult animals did not develop acute clinical disease and survived the HSV infection.

Animals↗

Epidermal intercellular relationships during carcinogenesis and cocarcinogenesis as revealed by scanning electron microscopy.

Investigations with the scanning electron microscope were carried out on the skin of 80 NMRI mice after treating them with small doses of the carcinogenic substance DMBA and the cocarcinogenic agent TPA, respectively. The results were correlated with histologic, transmission electron microscope and autoradiographic observations. The epidermis of TPA-treated animals was markedly hyperplastic with an orderly arrangement of cell layers. Autoradiographically only the basal cells were heavily labelled. With the scanning and transmission electron microscope a reduced number of intercellular connections and dilatation of the intercellular spaces could be detected. After treatment with DMBA the epidermis was only moderately hyperplastic but severely dysplastic with 3H-thymidine-labelled cells in the upper layers. The most characteristic findings were the loss of the intercellular connections, especially the lateral ones, and a pronounced dilatation of the intercellular spaces. The results obtained with the scanning electron microscope were quantified using morphometrical methods.

9,10-Dimethyl-1,2-benzanthracene↗