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D Komitowski

Publications and source records attributed to D Komitowski.

At least 37 records · Page 2Linked to original sources
PubMed1991

Regressing nude mouse grafts of Burkitt's lymphoma x lymphoblastoid cell hybrids show deregulation of the c-myc gene and expression of the EBV latent membrane protein.

Somatic cell hybrids between the malignant Burkitt lymphoma cell line BL 60 and the non-malignant Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) IARC 277 demonstrate the deregulated c-myc transcription pattern of the parental BL cell line during exponential growth in tissue culture. Subcutaneous nude mouse grafts of these hybrids, however, completely regress after an initial growth phase. To investigate whether regression of these grafts is mediated by a down-regulation of the BL-60-derived deregulated c-myc gene in vivo, c-myc transcription was analyzed in growing versus regressing hybrid grafts. In the initial growth phase as well as during regression, these grafts showed the deregulated c-myc expression pattern of the parental BL cell line with highly abundant c-myc transcripts originating from the BL specific translocation chromosome 8q+. Our results question the significance of c-myc deregulation for an unlimited in vivo growth potential of B-lymphoblastoid cells. To further characterize the hybrids, surface expression of B-cell-specific antigens was analyzed on the hybrids and shown to correspond to that of the parental LCL. In addition, transcription of the gene encoding for the EBV latent membrane protein (LMP) as well as histological features were analyzed in growing versus regressing hybrid grafts. The LMP gene, which is down-regulated in the tumors produced by the parental BL cells, was expressed in the hybrid grafts as well as in the parental LCL grafts. This finding might be compatible with a host response of the nude mouse against LMP. The histological analysis, however, which revealed massive necrosis in the center of the regressing grafts without pronounced inflammatory infiltrates, rather points to a hypoxemic process leading to graft regression.

Animals↗
PubMed1990

Quantitative features of chromatin structure in the prognosis of breast cancer.

In prognosis of breast cancer different parameters are in current use. Along with clinical staging the most important parameter appears to be histologic grading. Features of the grading such as nuclear pleomorphism proved to correlate closely with the proliferative activity and aggressiveness of the tumors. Because of difficulties in assessing and classifying the degree of nuclear pleomorphism by usual microscopy, the authors applied methods of digital image analysis. The study is a retrospective analysis of paraffine slides from the primary lesions of 60 breast cancers with 10 to 16 years of follow-up evaluation. Using large sets of different parameters defining nuclear morphology and chromatin structure the authors extracted criteria with prognostic importance. These included nuclear area in micron 2, eccentricity, integral optical density per micron 2, average area of a chromatin region, integral optical density of a chromatin region per micron 2, and the number of central chromatin regions per micron 2. The results demonstrate that the criteria used enable prediction of prognosis with an accuracy of 92%.

Breast Neoplasms↗
PubMed1989

Quantitative nuclear morphology in the diagnosis of ovarian tumors of low malignant potential (borderline).

Ovarian tumors of low malignant potential or of borderline malignancy are characterized histologically by the association of malignant type of epithelial proliferation with a noninvasive pattern of growth. Because epithelial proliferation relates to features of nuclear morphology and chromatin structure and because of the difficulties to distinguish nuclear atypism seen in borderline malignancy from that in frankly invasive tumors by usual microscopic study, the authors concentrated their studies exclusively on computerized analysis of cell nuclei images. Using specially developed methods of analysis the authors described geometrical, optical, and structural differences among the epithelial and stromal cell nuclei of benign, borderline, and malignant ovarian tumors. The structural differences concern the pattern of chromatin condensation and suggest that the cytokinetic properties of the borderline tumors are intermediate to those of benign and malignant. The results demonstrate that the quantitative evaluations provide objective and reproducible data useful in the differential diagnostic of the borderline malignancy.

Adenoma↗
PubMed1989

Quantitative aspects in defining prognostic factors of breast cancer.

Although many attempts have been made to define prognostic criteria, the long-term prediction of breast cancer prognosis remains a difficult task. In search of morphologic criteria with prognostic significance, we investigated 101 ductal invasive breast carcinomas by means of computerized image analysis. Our purpose was to define prognostic measures of the basic characteristics of breast cancers, growth rate and metastatic potential. Consequently, three principal types of analysis were performed: on Feulgen stained nuclei, on histological structures by using differential stainings and on desmosome-complexes revealed by immunofluorescence microscopy. The data obtained from analysis of the cell nuclei morphology and the chromatin structure served to establish objective nuclear grading. In comparison to the visual grading made during routine histology, the objective grading correlates better with the existence of lymph node metastases and with receptor status. The description of desmosome-complexes by using quantitative immunofluorescence microscopy indicates that in order to obtain relevant results, the histological pattern of the tumors has to be considered. In order to characterize these structures we introduced special methods of cluster analysis. The studies are an example of complex quantitative analysis of tumor morphology performed with different combined methods of microscopy and image processing.

Breast Neoplasms↗
PubMed1989

Behavioral endocrinology of male rats with periodic sexual contacts with exclusive or varied females.

Sexual contact keys a profound series of acute and chronic changes in males that, presumably, are orchestrated by acute pulsatile release of hormones. An experimental paradigm is reported in which male rats were paired periodically with either the same or different estrous females to receive identical amounts of copulatory experiences. Results confirmed the hypothesis that exposure to an unfamiliar female would induce a different endocrine response which would be reflected in various androgen-sensitive systems. The "successively polygynous" males showed more sexual behavior than "monogamous" males, and their respective females solicited the males differently, as well. Circulating levels of testosterone were higher immediately after sexual contact with an unfamiliar than with a familiar female partner. There were no differences in testosterone titers among the groups when the animals were killed at either 2 or 7 weeks after the final copulatory experiences. Yet, necropsies at 2 weeks postcopulation revealed that primary and secondary sex structures from polygynous males clearly were larger. Differences between the two experimental groups were reduced after 7 weeks of sexual rest, yet, polygnous males continued to show a different structural profile than the other groups. Conclusions were that males may experience greater activation of androgen-sensitive behavior and physiology following qualitatively different sexual contacts.

Adrenal Glands↗
PubMed1989

c-fos expression induces bone tumors in transgenic mice.

The proto-oncogene c-fos has been isolated as the cellular homolog of the v-fos gene found in the osteosarcoma inducing FBR- and FBJ-murine sarcoma viruses (MSV). Expression of the c-fos gene in transgenic mice leads to the development of bone lesions of which about half progress to bone tumors mainly chondrosarcomas. The tumors display a strong preference for males and have a latency with a mean of 9.5 months. However, also mice without visible lesions develop bone tumors with the same sex preference and latency. These consequences of c-fos expression are independent of the chosen promoter but dependent on a replacement of 3' noncoding sequences of c-fos by a long terminal repeat (LTR) of the FBJ-MSV virus.

Animals↗
PubMed1988

Structural changes in nuclear chromatin in rat pituitary after chronic stress of low intensity.

Acute, intense sources of "psychogenic" stress clearly modify the structure and function of the hypophysis, and there are concomitant changes in many peripheral physiological systems. Less dramatic sources of stress yield more equivocal results. An experiment is reported in which nuclear morphology of adenohypophyseal cells from 49 male rats exposed to a chronic, low-intensity stressor was examined both by conventional histological and computer-assisted-image-processing methods. The hypothesis tested was that an unequivocal pattern of morphological changes in the nucleus and nuclear chromatin would be revealed by image processing. Rats were killed after living for a year in a relatively low-stress environment, "crowded" in groups of five animals per cage. The control condition was a minimal stress environment of two rats per cage. Results suggested few signs of pathology from peripheral measures of hypophyseal activity, and direct light microscopic examination of the gland revealed no differences between the two groups. Analysis of computer-enhanced images of the pars distalis nuclei from the adenohypophysis, on the other hand, generated findings that were statistically and biologically significant. Nuclear size increased in the stress condition, the number of chromatin and area occupied by the particles increased, and the position of chromatin shifted toward the periphery of the nucleus. Perhaps more important, optical density analysis indicated that chromatin was less tightly packed in the experimental animals. Implications are that chronic, low-intensity stress modulates nuclear structural changes from a dormant to an active state that portend changes in the peripheral systems influenced by the hypophysis.

Adrenal Glands↗
PubMed1988

Various short-term assays and two long-term studies with the plasticizer di(2-ethylhexyl)phthalate in the Syrian golden hamster.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) and its main metabolite monethylhexylphthalate (MEHP) were investigated in several short-term in vitro assays, including mutagenicity in Salmonella typhimurium TA102, a strain sensitive to mutations arising as a cause of oxidative DNA damage. Also DNA amplification in SV40-transformed Chinese hamster cells and DNA damage in rat and hamster hepatocytes were investigated. The two compounds were not genotoxic in any of the test systems. Furthermore, DEHP was investigated in two long-term bioassays with Syrian golden hamsters using both i.p. (max. total dose 54 g/kg) and inhalative (7-10 mg/kg) application. In both experiments an additional group of animals received a combination treatment of DEHP with N-nitrosodimethylamine (NDMA). These studies were included in order to elucidate whether the observed influence of DEHP on the microsomal enzyme activity (Seth, 1982) may effect the carcinogenic activity of NDMA. There was no significant increase in tumor incidence after application of only DEHP via both routes. However, the occurrence of liver malignancies was significantly (P less than 0.001) reduced after the combination treatment in the inhalation study.

Air Pollutants↗
PubMed1988

Changes in tumor cell adhesiveness affecting speed of dissemination and mode of metastatic growth.

Adhesion variants can be isolated from suspension growing highly metastatic murine ESb tumor cells under reproducible conditions from uncloned as well as from cloned ESb tumor cells. One such variant, ESb-MP, has been analyzed in detail. In vitro it had similar growth properties and high invasive capacity as the parental ESb cells. In vivo, ESb-MP cells showed a reduced growth capacity as compared to ESb cells. This was seen at the site of tumor cell transplantation (increased latency period) as well as at the site of secondary tumor growth in internal organs. ESb-MP tumor cells disseminated much later than ESb cells from the primary tumor into the blood stream. Both tumor lines metastasized to the liver but they affected liver functions in a different way: ESb cells infiltrated the liver diffusely and exerted toxic effects on liver parenchyma very quickly. This resulted in early increase of liver enzyme activity in the blood. In contrast, liver infiltrated by ESb-MP cells showed a more focal type of colonization and the organs seemed to be functioning for much longer periods. In fact, animals inoculated with ESb-MP cells subcutaneously or intravenously had an increased life expectancy compared to ESb-tumor-bearing animals of about 300%. The organotropism of both tumor lines remained similar although there were kinetic and quantitative differences, especially with regard to the kidney. In late stages of tumor growth, ESb-MP-tumor-bearing animals developed a high percentage of metastases in the kidney and around and within the spinal cord, thereby causing a syndrome of hind-leg paralysis. This syndrome was remarkable in its reproducibility, especially after intravenous tumor cell inoculation. The changed adhesiveness thus seemed to have affected the tumor latency period, the speed of dissemination into blood and internal organs, the mode of organ infiltration (focal vs. diffuse) and of metastatic growth, parameters which all might contribute to the greatly reduced overall malignancy.

Animals↗
PubMed1987

Quantitative description of nuclear morphology in assessing resistance of sarcoma 180 to adriamycin.

Resistance to adriamycin generally is explained through changes of cell/drug interactions that possibly reflect structural alterations of intracellular targets. One of the main targets of adriamycin is believed to be nuclear chromatin. In order to recognize chromatin alterations, we studied cell nuclei morphology and chromatin structure by means of digital image analysis. The studies were performed in both adriamycin-sensitive and -resistant Sarcoma 180 cell lines which were cultured under growth-stimulated and nonstimulated conditions. Using specially developed methods, we extracted parameters characterizing geometrical, optical, and structural properties of the cell nuclei from light microscopical images. The latter parameters concerned microscopical appearances of condensed chromatin and were described by features of high-optical-density regions. The results demonstrated that the quantitative criteria applied enabled the discrimination of sensitive and resistant cells. The most important parameters are the nuclear size, number, distribution, and optical density of condensed chromatin regions. In addition, the criteria permit recognition of changes related to differences in the growth conditions of the cells. The data of the image analysis suggest that adriamycin resistance in Sarcoma 180 cells is associated with characteristic patterns of cell nuclear morphology which can be described with a sufficient number of appropriate parameters. The advantages of image analysis are evident when these results are compared with the flow cytometric findings. The conclusion is that structural features of nuclear chromatin provide information essential for the assessment of drug resistance.

Animals↗
PubMed1986

Quantitative analysis of the early changes of hepatocyte nuclei after treating Syrian golden hamsters with di(2-ethylhexyl)phthalate.

Although the biological action of phthalates has been widely discussed there is little information on early cellular changes indicative for toxic or carcinogenic effects. To study subtle alterations in the cell morphology, we have by means of image processing evaluated the nuclei of hamster hepatocytes after treatment with di(2-ethylhexyl)phthalate given in single i.p. doses of 30, 300, and 3000 mg/kg. The results indicate that by using specially developed methods for analysis of images of cell nuclei and chromatin structure, it is possible to recognize changes eluding detection with usual light microscopy.

Animals↗
PubMed1986

Changes of the elastin compartment in the human meniscus.

We report on the elastin, collagen and ground substance compartments in the human meniscus and their interrelationships. Elastin is found in neonates and shows both an arrangement parallel to the collagen fibre and into net-like structures. Branching, caliber inconstancy, rupture and the phenomenon of the "rubber band" are findings within the different forms of the meniscopathy. The function of the elastin compartment cannot be visualised without suggesting "puncta fixa". The morphology of the collagen-elastin-junctions has been described and their possible mode of function is discussed with the help of a model.

Adult↗
PubMed1986

Image analysis of hepatocyte nuclei in assessing di(2-ethylhexyl)phthalate effects eluding detection by conventional microscopy.

The effect of di(2-ethylhexyl)phthalate (DEHP) administered in single intraperitoneal doses of 30, 300 and 3000 mg/kg in Syrian golden hamsters was studied by means of routine pathologic investigations, electron microscopy and image analysis. The morphological evaluations did not show apparent differences between the control and treated animals. Such differences, however, were recognized by using image analysis. They concerned morphology of the hepatocyte nuclei and were defined by quantitative parameters reflecting geometrical, optical and structural properties. Of importance for differentiating dose/effect relationships were features of chromatin structure. In order to describe those features we developed special algorithms capable of identifying and characterizing regions of condensed chromatin as subimages. These were distinguished by their size, shape and optical density and showed typical distributions within the nucleus. As our results demonstrate, image analysis methods permit detection of DEHP related pathology in animals which, as far as is evident from routine morphologic evaluations, belong to the no-effect experimental group.

Animals↗
PubMed1985

Quantitative evaluation of heterochromatin in epithelial atypia by an image processing method.

Digital image analysis as a method enabling quantitative description of microscopical images is especially important in studying cellular atypia. However, by using that method for characterizing the complex chromatin structure and its changes during atypia considerable difficulties arise. Defining substructures of chromatin images we have developed new method for description chromatin structure based on locally adaptive thresholding. The results obtained suggest that typical for atypia are changes in the size, optical density and distribution of the high optical density regions (heterochromatin) identified within the cell nuclei.

Chromatin↗
PubMed1985

Quantitative description of chromatin structure during neoplasia by the method of image processing.

Nuclear chromatin is visualized by light microscopy as a mosaic of interchanging regions of low and high optical density (O.D.). The regions of high O.D. are well-defined as chromatin particles; features characterizing these particles enable the description of chromatin structure and the recognition of its changes during neoplasia. This paper presents a method of feature extraction by means of digital image analysis, based on a localization algorithm with locally adaptive thresholding. Although the chromatin particles varied greatly in their O.D., the algorithm enabled the identification of significant numbers of particles, which is essential in characterizing the complex architecture of chromatin. The results obtained by studying neoplastic nuclei and nuclei from control tissue suggest that the appearance of an additional class of chromatin particles, defined by their localization and optical density, is typical of chromatin changes during neoplasia.

Animals↗