scholarly journals Observations on Altered Hepatocellular Foci in National Toxicology Program Two-Year Carcinogenicity Studies in Rats

1989 ◽  
Vol 17 (4_part_1) ◽  
pp. 690-708 ◽  
Author(s):  
Takanori Harada ◽  
Robert R. Maronpot ◽  
Richard W. Morris ◽  
Gary A. Boorman

Retrospective characterization of morphological and stereological features of altered hepatocellular foci (AHF) in hematoxylin & eosin (H&E)-stained sections was performed on 6 conventional 2−yr carcinogenicity studies conducted in Fischer 344 (F344) rats by the National Toxicology Program (NTP). In 3 of these studies where there was clear evidence of hepatocarcinogenicity [1−amino−2,4−dibromoanthraquinone (ADBAQ), C.I. Acid Red 114, methyl carbamate], there was greater morphological variability in AHF than in the studies of chemicals that were not hepatocarcinogenic [4−hydroxyacetanilide, epinephrine, dimethoxane]. In addition to having the expected types of AHF, rats treated with ADBAQ, C.I. Acid Red 114, and methyl carbamate had atypical basophilic AHF. In addition, atypical eosinophilic AHF were present in rats treated with ADBAQ. Both types of atypical AHF showed a morphological spectrum and sequential changes suggesting they could develop into hepatocellular neoplasms. For the 3 liver tumor positive studies, there were dose-and time-dependent increases in stereological parameters for the atypical as well as commonly occurring clear, vacuolated, and mixed cell AHF. Consistent stereological changes were not found for commonly occurring basophilic and eosinophilic AHF. Aside from some decreases in stereological measurements in some rats treated with 4−hydroxyacetanilide and epinephrine, there were no significant quantitative changes in AHF in the three liver tumor negative studies. These results show that hepatocarcinogens may induce unique types of AHF in conventional 2−yr carcinogenicity/toxicity studies in rats and may cause quantitative increases in commonly occurring clear, vacuolated, and mixed cell AHF. Such qualitative and quantitative changes are potentially useful predictors of hepatic neoplasia.

1989 ◽  
Vol 17 (4_part_1) ◽  
pp. 579-593 ◽  
Author(s):  
Takanori Harada ◽  
Robert R. Maronpot ◽  
Richard W. Morris ◽  
Katherine A. Stitzel ◽  
Gary A. Boorman

Quantitative evaluation of altered hepatocellular foci (AHF), followed by stereological analysis was performed on standard hematoxylin and eosin-stained liver sections from control Fischer 344 (F344) rats of both sexes from seven 2-yr carcinogenicity studies conducted by the National Toxicology Program (NTP). Liver samples were collected at 6, 9, 12, 15, 18, and/or 24 months on study. Although AHF had a broad spectrum of morphological features, they could be classified into the following 5 types using previously published criteria: basophilic, eosinophilic, clear, vacuolated, and mixed cell foci. Approximately 50% of the animals had foci at 6 months, and the incidence reached nearly 100% at 15 months in both sexes. The number, size and volume fraction of AHF increased with age in both sexes; these changes were most evident for basophilic and clear cell foci. The number of basophilic foci was significantly greater in females than in males while clear cell foci were more numerous in males. This sex difference was observed at each time point. Mean number of all types of AHF in males and females at 24 months was 547 and 460 per cubic centimeter of liver, respectively. Despite the high incidence of AHF in control rats, the incidence of hepatocellular neoplasms is low. The implication is that most foci do not progress to neoplasia in control F344 rats used in 2-yr studies.


Author(s):  
Roberto Bassani ◽  
Enrico Ciulli ◽  
Enrico Manfredi ◽  
Salvatore Manconi ◽  
Alessandro Polacco ◽  
...  

This work presents some of the results obtained from an extensive experimental test campaign performed at the Department of Mechanical Nuclear and Production Engineering (DIMNP) of Pisa University with the partnership of Avio Propulsione Aerospaziale S.p.A. This test campaign, that is still being performed, is concerned with the characterization of teeth damage in high performance gear transmissions, such as aeronautical ones, characterized by high levels of velocity and load. Damage detection and monitoring have been pursued during all the tests in order to achieve a better understanding of causes and evolution of teeth damage. Moreover, to investigate the effects of different parameters on teeth damage, tests with different load, velocity, teeth geometry, materials and surface finishing, have been performed. The surface conditions of the gear teeth have been investigated using in particular two different instruments: a computer-controlled stylus profilometer able to perform 3D investigations and a scanning electron microscope (SEM) recently provided by a software for surface reconstruction. Qualitative and quantitative changes in surface roughness have been detected. Besides the experimental activity, numerical analyses have been also started for finding theoretical criteria for surface damage prediction; some few obtained results are presented. Due to the vastness of the work performed, only a survey of the main results obtained till now is presented in the paper.


1989 ◽  
Vol 17 (4_part_1) ◽  
pp. 675-684 ◽  
Author(s):  
Robert R. Maronpot ◽  
Takanori Harada ◽  
A. S. K. Murthy ◽  
Gary A. Boorman

Altered hepatocellular foci (AHF) can be reliably identified in hematoxylin and eosin (H&E)-stained sections of liver from interim and final sacrifice intervals in 2-yr carcinogenicity studies in rats. While most AHF can be categorized on the basis of a defined set of descriptive terms, viz., basophilic, eosinophilic, clear, vacuolated, and mixed foci, exposure to hepatocarcinogenic agents may induce unique types of AHF which should be distinguished from those that occur more commonly. It is proposed that unique treatment-associated AHF be classified as atypical AHF and that they be completely described in the pathology narrative accompanying the study. Since profound changes in the number and size of AHF have been documented in Fischer 344 rats with mononuclear cell leukemia, it is recommended that liver focus data from leukemic animals be censored in assessing potential effects of treatment on AHF. At the present time, there are insufficient data to allow routine use of AHF in regulatory decision-making in the absence of a liver tumor response. However, such data may form part of weight-of-evidence considerations used by regulatory bodies when accompanied by a concomitant liver tumor response.


2021 ◽  
Author(s):  
Caitlin F Fowler ◽  
Dana Alexander Goerzen ◽  
Dan Madularu ◽  
Gabriel A Devenyi ◽  
Jamie Near ◽  
...  

Animal models are widely used to study the pathophysiology of disease and to evaluate the efficacy of novel interventions, crucial steps towards improving disease outcomes in humans. The Fischer 344 (F344) wildtype rat is a common experimental background strain for transgenic models of disease and is also one of the most frequently used models in aging research. Despite frequency of use, characterization of neuroanatomical change with age has not been performed in the F344 rat. To this end, we present a comprehensive longitudinal examination of morphometric change in 73 brain regions and at a voxel-wise level during normative aging in a mixed-sex cohort of F344 rats. We identified age- and sex-related changes in regions such as the cortex, hippocampus, cingulum, caudoputamen, and nucleus accumbens, which are implicated in memory and motor control circuits frequently affected by aging and neurodegenerative disease. These findings provide a baseline for neuroanatomical changes associated with aging in male and female F344 rats, to which data from transgenic models or other background strains can be compared.


Author(s):  
Leandro C. GAETANO ◽  
Fernando ABDALA

We surveyed the stapedial anatomy of Thrinaxodon liorhinus Seeley, 1894 and Galesaurus planiceps Owen, 1859, two iconic Early Triassic basal cynodonts. The complete characterization of this bone and the analysis of its morphological variability along the ontogeny within each taxon were possible through the study of eleven elements of Thrinaxodon Seeley, 1894 and nine of Galesaurus Owen, 1859. Our results highlight notable qualitative and quantitative differences among specimens of the same species. Stapes growth model in Galesaurus shows a positive allometry on the lateromedial length and on the anteroposterior width, whereas in Thrinaxodon there is a negative allometry in the anteroposterior width but the lateromedial length is isometric. This study offers a counterintuitive result of inordinate high intraspecific morphological variation of the stapes of basal non-mammaliaform cynodonts.


2019 ◽  
pp. 86-95
Author(s):  
Amal Aithida ◽  
Abdelghani Tahiri ◽  
Youssef Oubassine ◽  
Kalil Cherifi ◽  
Mimoun Mokhtari ◽  
...  

Rosa damascena perfume rose has a considerable place in Morocco. The essential oil, hydrolate (rose water) and dried buds produced in Kalâa Mgouna are intended for export. However, local varieties are not identified. Hence, the objective of our research into the identification of morphological variability by studying 15 qualitative and quantitative characteristics related to leaf, spine and flower at eight localities along the valley of roses. The present study has demonstrated the existence of a great morphological variability within the Kalâa Mgouna’s perfume rose. The characters associated with leaves and spines drive this variability. The PCA analysis identified four morphotypes; the morphotype I whose stems are unarmed, the morphotype II characterized by broad leaves and moderately spiny stems, the morphotype III having stems bearing long spines and whose petals are wider. Finally, the morphotype IV characterized by very thorny stems, leaves of reduced size and whose petals are wider.


Author(s):  
R.L. Price ◽  
T.K. Borg ◽  
L. Terracio ◽  
M. Nakagawa

Little is known about the temporal expression of extracellular matrix components (ECM) and its receptors during development of the heart. Recent reports have shown that ECM components undergo both qualitative and quantitative changes during development, and it is believed that ECM components are important in the regulation of cell migration and cell:cell and cell:ECM recognition and adhesion.Integrins are transmembrane glycoproteins which bind several ECM components on their external face and cytoskeletal elements on the cytoplasmic face. Laminin is a basement membrane component which has been recognized as an important site for cell adhesion. Both the integrins and laminin are expressed early in development and continue to be expressed in the adult heart. With their documented roles in cell recognition, and cell:cell and cell:ECM migration and adhesion these proteins appear to be important components in development of the heart, and their temporal expression may play a pivotal role in morphogenesis and myofibrillogenesis of the heart.


2002 ◽  
Vol 46 (5) ◽  
pp. 425
Author(s):  
Ki Bong Yu ◽  
Myung Kwan Lim ◽  
Hyung Jin Kim ◽  
Jun Soo Byun ◽  
Young Kook Cho ◽  
...  

Author(s):  
Bugero N.V. ◽  
Ilyina N.A. ◽  
Aleksandrova S.M.

In order to understand the structure and dynamics of symbiotic relationships of human intestinal biotope micro-organisms, taxonomic constancy indices, the degree of contagion of the biocenosis under study and floristic significance were investigated, which made it possible to detect qualitative and quantitative changes in the microecology of the biotope being studied in persons living in different ecologically heterogeneous territories of Saint Petersburg. The contagiosity index estimated the distribution of species in space. Persons living in the ecologically disadvantaged Kirov district of the city have been found to show a reliable increase in this indicator for the obligate microflora: bifido and lacto bacteria, intestinal columns and bacteroids, compared to the resort district, which is considered a relatively favourable area for residence. On the contrary, there has been a reliable decrease in this indicator in the group of opportunistic micro-organisms (fungi of the genus Candida, staphylococcus, clostridium, etc.), resulting in the liberation of ecological niches successfully occupied by transient flora. This ratio reveals an imbalance of participation in the horizontal structure of the intestine ecosystem of the main symbiotes and representatives of the transient flora. To analyse the structure of symbiotic relationships, the constancy indices that form the microflora of the individuals of the groups studied were investigated. The analysis of the data obtained suggested that the dominant species in both groups were optional-anaerobic bifido and lactobacteria and oblique-anaerobic bacteroids. It should be noted, however, that in the residents of the dysfunctional Kirovsky district, against the background of the reduced constancy of the normal flora, opportunistic micro-organisms have entered. The floral significance index was also declining in the obligate flora of this group and increased for opportunistic species. Thus, the study of the environmental characteristics of the intestinal biotope using different ecological parameters for persons living in different technogenic load regions of St. Petersburg has shown that in the Kirov district with an unfavourable environmental situation there are compensated qualitative and quantitative changes in the intestinal microbiocenosis, resulting in a change in the hierarchy in the overall structure of micro-organisms.


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