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R A Ettlin

Publications and source records attributed to R A Ettlin.

10 recordsLinked to original sources
PubMed1992

Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative Leydig cell alterations in rats.

Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations.

Adenoma↗
PubMed1991

A brief review of modern toxicologic pathology in regulatory and explanatory toxicity studies of chemicals.

Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics.

Animals↗
PubMed1991

Morphologic and immunohistochemical characterization of Leydig cell tumor variants in Wistar rats.

During a routine long-term drug safety study, lasting approximately 2 1/2 yr, male Wistar rats, treated with a prolactin-inhibiting compound, developed an excess of Leydig cell tumors (LCTs). Most tumors were typical for the rat but a small number showed an unusual variation and some appeared malignant. The variation consisted of glandular and/or tubular structures within the tumor mass which occasionally anastomosed and contained an eosinophilic periodic-acid Schiff (PAS) positive material. In a few of these variants, malignant features such as cellular atypia, capsular, and lymphatic invasion and necrosis were seen. No metastases were detected. Detailed morphological and immunohistochemical investigations were conducted in order to establish the cell of origin of these variants. Glandular/tubular structures were found to stain with varying intensity for vimentin and cytokeratin, but were always negative for beta-tubulin. The results indicated that the cell of origin of these LCT variants was indeed the Leydig cell and that glandular and/or tubular structures within LCTs represented a form of Leydig cell metaplasia.

Animals↗
PubMed1987

Differential susceptibility of immature rat testes to doxorubicin at critical stages of maturation. Biochemical and functional assessment.

The toxic effects of doxorubicin on the reproductive system of the male rat were studied at different susceptible stages of postnatal development. A multidisciplinary approach including the assessment of histopathological, functional and biochemical parameters was chosen. Groups of male rats were treated once with the compound (3 mg/kg) on postnatal day 6, 16, 24 or 45. Both the onset of reproductive capacity and fertility were determined by serially mating ten animals per group for 12 weeks beginning at the age of 45 days. Reproductive organ weights, sperm counts and epididymal androgen binding protein (ABP) were measured at intermediate (80-day-old rats) or terminal sacrifice (129-day-old rats). Age dependent differential doxorubicin toxicity was evident. Treatment of 6-day-old animals with doxorubicin severely impaired development of reproductive functions. Treatment of 16-day-old animals reduced fertility throughout the mating study, as well as body and reproductive organ weights and sperm counts. Initial toxicity was observed in the group treated at 24 days of age; particularly, low reproductive organ weights and low sperm counts were found. These findings proved reversible towards the end of the study. Neither biochemical nor functional impairment of the reproductive system could be observed in the group treated at 45 days of age.

Animals↗
PubMed1987

Morphometry and immunocytochemistry.

The use of morphometry (and stereology), especially in conjunction with immunocytochemistry, in surgical and experimental pathology is reviewed. The combined use of morphometry and immunocytochemistry permits the study of secretory products and the distinction between cells that produce them, e.g., as in the pancreas. Several examples to illustrate the application of immunocytochemical techniques in morphometry are presented. For example, using this approach on the pancreas, it was shown that not only B cells, but also A and D cells, seem to undergo pathologic changes in a prediabetic organism. Since morphologic alterations may be distributional as well as quantitative, a model for the assessment and statistical evaluation of the distribution of objects within an area is discussed. Similar procedures were used to analyze the distribution of cytochrome P-450 molecules along intracellular membranes; however, special labeling techniques were necessary for this quantification in the electron microscope. Immunoenzyme cytochemically stained secretions can also be studied morphometrically, and microdensitometry and microfluorometry can also be used to quantify immunocytochemical reactions, as is shown in the analysis of the intralobular distribution of NADPH-cytochrome P-450 reductase in the rat liver. Finally, the BIVAS semiautomatic system for morphometric measurements, developed at the Department of Pathology of the University of Basel, is briefly described.

Animals↗
PubMed1986

Retardation of spermiation following short-term treatment of rats with theobromine.

Groups of 4-6 Fü-albino rats were examined 24 h after 3 daily doses of 500 mg/kg bw of theobromine administered orally by gavage as well as 1, 2, 4, 6, and 10 weeks after 5 daily doses. Controls received the standard solvent vehicle (SSV) only. A variety of parameters were assessed including body and organ weights, serum clinical chemistry, hematological parameters, epididymal sperm motility and LDH-X fraction in seminal plasma, serum gonadotropins and testosterone, and the morphology of various organs. Testes were perfused with 5% glutaraldehyde and semi-thin sections were evaluated. The most striking morphological observation was a retarded release of late spermatids into the tubular lumen mainly 2 weeks post treatment. This partial disruption of the rigid spermatogenic synchronization was not followed by substantial germ cell death. The other parameters investigated remained relatively normal throughout the study. These observations suggest that theobromine at the dose tested rather selectively interferes with germ cell kinetics. Sertoli cell toxicity could account for these early and subtle effects as well as for the late and severe effects of subchronic exposure of rats to theobromine as reported in the literature.

Animals↗
PubMed1985

Testicular toxicity of antineoplastic drugs during postnatal development of the rat.

A multidisciplinary approach was chosen to assess effects of anticancer drugs on the postnatally developing reproductive system. Male rats were treated once with doxorubicin (3 mg/kg bw i. p.) on either postnatal day 6, 16, 24, or 45. Mating studies, sperm counts, estimation of androgen binding protein and assessment of pathological parameters were performed at the time of onset of reproductive capacity of the controls and for 12 weeks thereafter. Male reproductive toxicity of doxorubicin was clearly dependent on the age at the time of treatment, being greatest for 6 day old animals and absent for 45 day old animals.

Androgen-Binding Protein↗