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H Zerban

Publications and source records attributed to H Zerban.

At least 37 records · Page 2Linked to original sources
PubMed1990

Echographic tissue characterization in diffuse parenchymal liver disease: correlation of image structure with histology.

Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization.

Fatty Liver↗
PubMed1990

Computerized ultrasound B-scan texture analysis of experimental fatty liver disease: influence of total lipid content and fat deposit distribution.

Statistical pattern recognition procedures allow a quantitative description of ultrasound-B-scan image texture. According to well-established animal models, different types of fatty liver disease were induced in female Wistar rats. For the correlation of the computerized ultrasound image with its underlying histology a variable tissue model based on histomorphological data, texture analysis of the histological image and biochemical measurements of total lipid, water and hydroxyproline content was created. Whereas a regional arrangement of large fat deposits leads to a significant increase in the "mean grey level" (measure of image brightness) of the ultrasound-B-scan image, there is no difference in image brightness between normal liver tissue and liver steatosis for the tissue model with diffuse homogeneous fatty infiltration. It is demonstrated by multiple linear regression analysis that the "mean grey level" of the ultrasound-B-scan image depends not only on total lipid content but even more on the histomorphological fat deposit distribution.

Animals↗
PubMed1989

Sequential changes in growth kinetics and cellular phenotype during hepatocarcinogenesis.

Sequential changes in cell proliferation and cellular phenotype during hepatocarcinogenesis induced in rats with N-nitrosomorpholine were investigated by autoradiographic determination of the [3H]thymidine-labelling index in morphologically defined focal lesions and extrafocal hepatic tissue at different times between 4 and 48 weeks after withdrawal of the carcinogen (stop model). The labelling index was found to be significantly increased in all types of preneoplastic and neoplastic hepatic lesions as compared to both the liver tissue of untreated controls and the extrafocal parenchyma of N-nitrosomorpholine-treated rats. However, the extent of the increase in labelling index differed in the phenotypically diverse types of preneoplastic and neoplastic lesions. There was a significant but relatively small increase in the labelling index in clear and acidophilic cell foci. A much stronger elevation of cell proliferation was characteristic of mixed and basophilic cell foci. The development of hepatocellular adenomas and carcinomas from preneoplastic hepatic foci was further characterized by an additional increase in cell proliferation. Each specific cellular phenotype was associated with a rather uniform proliferation rate, which remained elevated at all time points studied, suggesting that the rate of cell proliferation in the phenotypically diverse preneoplastic hepatic foci mainly reflects the intrinsic growth potential of the respective cellular phenotypes. The results support the concept that the predominant sequence of cellular changes in hepatocarcinogenesis induced by the stop model leads from the clear and acidophilic cell foci, storing glycogen in excess, through mixed and basophilic cell foci to hepatocellular adenomas and carcinomas. The fact that the labelling index of the extrafocal liver tissue of N-nitrosomorpholine-treated rats was also significantly higher than that of the normal parenchyma of untreated controls might indicate an involvement of extrafocal hepatocytes, in addition to that of foci of altered hepatocytes, in hepatocarcinogenesis.

Animals↗
PubMed1989

Ultrastructural and immunocytochemical characterization of the cellular phenotype in primary adenoid liver tumours of the rat.

The cellular phenotype of 34 primary adenoid liver tumours induced in rats with N-nitrosomorpholine was studied by immunocytochemical and electron microscopical methods in order to elucidate the histo- and cytogenesis of these tumours. Three types of ducts were distinguished in the adenoid liver tumours at the ultrastructural level being characterized as of hepatocellular, transitional and cholangiocellular phenotype. The transitional cells took an intermediate position between the hepatocellular and the cholangiocellular phenotype. Frequent features of the hepatocyte-like differentiation were large round nuclei with a dispersed chromatin, glycogen-associated ER complexes, peroxisomes and the formation of bile canaliculi. Evidence for the relationship to bile ductular cells was provided by the regular association with a basement membrane, the (inconstant) positive immunohistochemical reaction for cytokeratin polypeptide KA-4, a poorly developed ER and small mitochondria. An additional finding in the ducts with a transitional cellular phenotype was the selective accumulation of mast cells integrated into the epithelium. Intimate associations between cells of the hepatocellular, transitional and cholangiocellular phenotype were observed at the light and electron microscopic level. The results suggest that a transdifferentiation (metaplasia) from cells with a hepatocellular to those with a transitional or cholangiocellular phenotype takes place in many liver tumours.

Adenoma↗
PubMed1989

[Quantitative studies on the influence of connective tissue and fatty structures on the ultrasonic image of the liver].

Using a computerized ultrasound system, 63 autopsied livers were examined. A quantitative description of the ultrasound image was made by using statistical parameters from pattern recognition algorithms. As a reference a chemical/morphometrical classification into normal, diffuse and regional fatty infiltration and fibrosis/cirrhosis was performed. Diagnostic accuracy varied from 77% to 92%. Ultrasound tissue characterisation showed an influence of fatty and connective tissue structures on image parameters. This supplies evidence for the fact that computerised ultrasound examination yields more information from the ultrasound image than the normal observer. This may be the cause of an increased diagnostic accuracy when using computerized ultrasound systems, especially in the case of fibrosis/cirrhosis.

Diagnosis, Computer-Assisted↗
PubMed1989

[Computer-assisted ultrasonic B-scan texture analysis of experimental liver tumors].

Primary liver cancer has been induced experimentally in female Wistar rats by diaminoazobenzene intoxication or subcapsular liver implantation of Novikoff cell suspensions. The ultrasonic B-scan image of these malignant tumours are described via statistical texture parameters in respect of image brightness, microtexture and macrotexture. A discrimination of the tumour texture profiles is possible with an accuracy of about 80%. There are correlations between ultrasonic image parameters and histomorphological tissue components but there is no specific link between the histological tumour-type and these B-scan data.

Animals↗
PubMed1989

Significance of sequential cellular changes inside and outside foci of altered hepatocytes during hepatocarcinogenesis.

A variety of phenotypic cellular changes emerge in the liver of different species prior to the appearance of hepatocellular adenomas and carcinomas induced by carcinogenic agents (chemicals, radiation, hepadna viruses) or develop "spontaneously." Foci of altered hepatocytes have been studied most extensively in rats treated with chemical carcinogens; they are considered preneoplastic lesions and have been used in several laboratories as endpoints in carcinogenicity testing. The principles and problems of the morphological classification of foci of altered hepatocytes are presented. In addition to the 4 types of foci generally accepted (clear, acidophilic, basophilic and mixed cell foci), further subtypes (intermediate cell foci) or other types of foci, namely tigroid cell foci and amphophilic cell foci, have more recently been separated as distinct pathomorphological entities. Whereas the amphophilic foci might result from a modulation of clear and acidophilic cell foci, the tigroid cell foci apparently represent a stage in a separate cell lineage leading to hepatocellular adenomas. It remains open whether the tigroid cell foci may also progress to carcinomas. Extrafocal phenotypic changes of hepatocytes might also be involved in hepatocarcinogenesis. The cellular phenotypes within foci also depend strongly, among many other factors, on the dose and duration of the carcinogenic treatment. Cytomorphological, cytochemical, microbiochemical and stereological studies suggest that the predominant sequence of cellular changes during hepatocarcinogenesis leads from the clear and acidophilic cell foci storing glycogen in excess through mixed cell foci and nodules to basophilic cell populations prevailing in hepatocellular carcinomas. A multitude of metabolic aberrations is associated with the sequential cellular changes. Aberrations in carbohydrate metabolism are particularly prominent and might be causally related to the neoplastic transformation of the hepatocytes.

Animals↗
PubMed1989

[Cytology and cytogenesis of experimental epithelial kidney tumors].

Nearly all types of epithelial kidney tumors known from human pathology may be induced by chemicals in laboratory animals. Using cytological criteria at least four different tumor types, namely clear/acidophilic (granular) cell tumors, chromophobic and basophilic cell tumors, and oncocytomas may be distinguished. In rats treated for limited time periods (stop experiments) with nitrosamines or streptozotocin, these different tumor types frequently developed concomitantly in the same kidney and bilaterally. The appearance of all types of epithelial tumors was preceded by specific tubular alterations. The preneoplastic tubular alterations emerged after long lag periods; they were characterized by a phenotypic conversion of the renal epithelia. There was no indication of an increased cell proliferation during the period of carcinogen administration under the conditions of the stop experiments used. Four types of preneoplastic tubular lesions could be distinguished each of which appeared to be related to the development of a certain cytogically well defined tumor type: 1. Chromophobic cell tubules sometimes storing glycosaminoglycans; they developed from the proximal nephron and apparently were prestages of chromophobic, perhaps also basophilic tumors, 2. basophilic cell tubules frequently containing small amounts of glycosaminoglycans; they also developed from proximal tubules and are considered precursors of basophilic cell tumors, 3. oncocytic tubules preceded the appearance of oncocytomas; they originated from the collecting duct system and were composed of cells crowded with mitochondria, and 4. clear cell tubules storing glycogen in excess; they also appeared to develop predominantly, if not exclusively, from the collecting duct system and gave rise to clear/acidophilic cell tumors which frequently accumulated lipids, most probably glycolipids, in addition to glycogen. The results of enzyme histochemical and biochemical studies on the different types of preneoplastic and neoplastic renal lesions suggest that neoplastic cell transformation in renal epithelia is closely related to a basic shift in energy metabolism.

Animals↗
PubMed1988

Quantitative morphometric comparison between the expression of two different "marker enzymes" in preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine.

Male Sprague-Dawley rats were treated with low doses of N-nitrosodiethanolamine (NDELA) (0.2, 0.63, 1.5, 6 and 25 mg/kg body wt per day). Foci of altered hepatocytes developed at all dose levels. The extent of foci positive for gamma-glutamyl transpeptidase (gamma-GT), as demonstrated histochemically in frozen sections, was quantitated morphometrically and compared with the data obtained earlier in the same livers by measuring the extent of foci positive for glucose-6-phosphate dehydrogenase (G6PDH). The area density of foci positive for gamma-GT was much smaller than that of foci positive for G6PDH at all dose levels and time points studied. However, there was an increase in the area density of both gamma-GT- and G6PDH-positive foci proportionally to the time of treatment and the total dose of the carcinogen administered. The dose-time relation for the induction of 0.5% gamma-GT positive liver tissue assessed as a double logarithmic plot gives a straight line. The same holds true for the induction of 1% G6PDH-positive liver tissue. The slopes of these straight lines are identical, and they have the same characteristics as the line indicating the time when 50% of the animals developed liver tumors at higher doses. Thus, a close statistical correlation of enzyme altered hepatic foci and the development of hepatocellular tumor exists irrespective of the absolute amount of the area density of the respective foci.

Animals↗
PubMed1988

Dose-time relationship of the development of preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine.

The carcinogenic efficiency of very low doses of N-nitrosodiethanolamine (NDELA), an N-nitroso compound of environmental significance, was assessed by administering it to male Sprague-Dawley rats at five different dose levels: 0.2, 0.63, 1.5, 6 and 25 mg/kg b.w./day in the drinking water. Quantitation of the numbers and size of liver foci positive for glucose-6-phosphate dehydrogenase (G6PDH) by morphometric methods revealed a good correlation between the dose and duration of carcinogen treatment and the extent of G6PDH-positive foci development. Thus the area density increased proportional to time and dose. The dose-time relation for the induction of 1% G6PDH-positive liver tissues assessed as a double logarithmic plot gives a straight line with the same characteristics as that which results when the induction of liver tumors is evaluated.

Animals↗
PubMed1987

Renal oncocytoma: origin from the collecting duct.

The histo- and cytogenesis of two cases of renal oncocytoma have been studied by cytomorphological and cytochemical methods. Transitions from collecting ducts into oncocytic tubules were observed at the light and electron microscopic levels. The fine structure of the oncocytes in tubules and tumors is described in detail. Cytochemically, the oncocytic tubules and oncocytomas share many characteristics with the distal nephron, especially the collecting ducts. A striking difference is the enhanced activity of succinic dehydrogenase which corresponds to the increase in the number of mitochondria in oncocytes. All the results suggest that renal oncocytoma originates from the collecting duct.

Adenoma↗
PubMed1987

Combination experiments with very low doses of three genotoxic N-nitrosamines with similar organotropic carcinogenicity in rats.

The study was designed to assess the syncarcinogenic activity of very low doses of N-nitrosodiethylamine (NDEA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiethanolamine (NDElA) in the liver of 1800 male Sprague-Dawley rats. The N-nitrosamines were administered throughout the rats' lives individually and in combination at three logarithmically spaced dose levels contained in drinking water. The dose levels in the individual dose-response experiments ranged from the lowest concentrations of previous experiments (NDEA, 0.1 mg/kg; NPYR, 0.4 mg/kg; NDElA, 2.0 mg/kg) to dosages 10 times lower and comprised a high, medium and low dose (escalation factor: 3.16). The high dose of the combination contained the three nitrosamine concentrations used as the medium doses of the individual nitrosamines. The medium combination dose resulted from the combined administration of the three lowest dosages, and the low combination dose consisted of three nitrosamine dosages which amounted to one-third of the low dosages respectively. Administration of these dosages was associated with a dose-dependent incidence of liver cancer: NDEA induced 45, 3.8 and 2.5%; NPYR caused 21.3, 5 and 1.3%; NDElA generated 7.5, 1.3 and 2.5%; and the combinations induced 16, 4.2 and 1.7% respectively. Untreated controls showed 0.6% liver cancer incidence. Besides the liver, the gastrointestinal tract, the neurogenic tissue, the urinary tract and the hematopoietic and lymphatic tissue were affected by tumor incidences increased over that of controls. There was, however, no well-defined dose dependency as with the liver tumors. These results indicate dose dependency of liver tumor formation even at very low exposure levels of the individual agents. The carcinogenic effects of the hepatotropic N-nitrosamines summed up in combination. The observed additivity was linear. Dose levels, which alone would presumably not have been carcinogenic, effected a significant cancer risk in combination.

Animals↗
PubMed1986

Aberrant regulation of carbohydrate metabolism and metamorphosis during renal carcinogenesis.

Systematic studies of the sequence of cellular changes during renal carcinogenesis induced in rats by stop experiments with N-nitrosomorpholine or streptozotocin and of human renal cell carcinomas led to the following main results and conclusions: All types of epithelial kidney tumors known from human pathology, namely clear-cell, acidophilic (granular), basophilic, chromophobic and oncocytic tumors, can be induced by the chemicals. Phenotypically altered epithelia resembling those in the tumors appear in single or multiple tubules long before unequivocal tumors develop. The progression from the preneoplastic tubular lesions to the tumors is an autogenous process which is independent of the further action of the carcinogen. At least three different types of tubular lesions can be distinguished: (a) Clear cell tubules storing glycogen in excess, (b) chromophobic or basophilic tubules frequently accumulating acid mucopolysaccharides (glycosaminoglycans, proteoglycans), and (c) oncocytic tubules accumulating atypical mitochondria. Whereas the precise site of origin of the clear cell tubules within the nephron remains unclear, the fine structural and cytochemical findings suggest that the chromophobic and basophilic tubules originate from the proximal and the oncocytic tubules from the distal nephron. Each type of tubular lesion is apparently the precursor of a cytologically specific tumor type. The well-known aberration in carbohydrate metabolism in renal tumors might occur in response to a carcinogen-induced metabolic derangement which is frequently associated with excessive storage of polysaccharides or lipids persisting for weeks and months until fast-growing tumors appear. Whereas the primary biochemical lesion leading to the persisting storage phenomena is most probably fixed at the genetic level, epigenetic changes, namely an adaptation of cellular enzymes gradually activating alternative metabolic pathways, might be responsible for the ultimate neoplastic transformation of the cell.

Adenoma↗
PubMed1983

Spongiosis hepatis in rats treated with low doses of hepatotropic nitrosamines.

Spongiosis hepatis, a characteristic pathomorphologic entity originating from the perisinusoidal liver cells, was observed in rats after administration of relatively low doses of the hepatocarcinogens dimethylnitrosamine (DMNA) and nitrosopyrrolidine (NO-Pyr), but not after application of the urinary bladder carcinogen butyl-butanolnitrosamine (BBNA). The results support the conception that spongiosis is a persisting liver lesion due to specific changes of the perisinusoidal liver cells by hepatotropic carcinogens.

Animals↗
PubMed1982

The cytoskeleton in tumor cells.

During the past few years several laboratories investigated the occurrence of cytoskeletal components in epithelial and mesenchymal cells by electron microscopy and/or immunocytochemical methods in a number of tumor types growing in vitro or in the body. Since it is well established that antibodies to different intermediate-sized filament proteins can distinguish cells and tissues of epithelial, mesenchymal, muscle, astrocytic and neural origin special attention has been paid to the behaviour of these filaments in neoplastic cells recently. While the organisation of the cytoskeleton in tumor cells growing in vitro is very variable, regularities relevant for the diagnosis and the determination of the histogenetic origin of tumors have been observed in tumor cells growing in the body. In general, ultrastructural and immunological features of intermediate filaments are maintained during neoplastic transformation in the body. Thus immunofluorescence microscopy with antibodies to cytoskeletal proteins is a powerful tool for the classification and differential diagnosis of tumors, especially for the distinction between epithelial and mesenchymal tumors, including metastases. The concept that presence of an excess of contractile proteins such as actin is an important prerequisite for the metastatic spread of malignant cells has not been unequivocally supported by more recent results. However, an accumulation of various types of intermediate filaments (e.g. prekeratin, vimentin, acidic glial fibrillar protein) has been shown in different tumor types. The further elucidation of this alteration could contribute to a better understanding of the molecular mechanisms of neoplastic cell transformation.

Adenoma, Bile Duct↗