Experimentelle Pathologie最新文献

The modifying influence of atropine and reserpine on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) induction of stomach tumors was studied in experiments on 120 randombred male white rats. At the same time, pharmacological analysis of the mechanism of the carcinogenic action of MNNG was carried out. Atropine stimulated and reserpine markedly inhibited the carcinogenic effect of MNNG. MNNG interference altered the specific effects of amphetamine and phenobarbital. These alterations are due to the MNNG damage of the permeability of the presynaptic membrane of the central adrenergic structures. The leading role of adrenergic influences on the processes of carcinogenic transformation of stomach cell processes is discussed.

Two human pheochromocytomas were cultured for long periods. One was cultured for a year, the other is still growing after a cultivation time of seven months. Though decreasing with the age of cultures the cells contained catecholamines all the time. Catecholamines were demonstrated by electron microscope, by fluorescence histochemistry and by Vulpian's and Da Prada's methods. Both pheochromocytomas were responsive to Nerve Growth Factor and showed dose-dependent development of neurite-like processes.

Tumors from patients with breast cancer were examined by light microscopy using immunoperoxidase techniques. The positive immunoperoxidase reaction was observed in 12 of 19 tumors treated with autologous serum. The percentage of the labeled tumor cells was from 10–15 to 60–70. It was established that tumor cell-associated antigen(s) was located mainly on both, the plasma and the nuclear membrane. More rarely it could be seen on the chromatin.

Histochemical and histopathological changes in the skin of rats, after the daily application of manganese chloride solution for a period of 90 days, are reported. These alterations consist of hyperkeratinization and marked proliferation of hair follicles. The application of manganese chloride solution produced marked inhibition in the activities of succinic dehydrogenase, glucose-6-phosphate dehydrogenase and cytochrome oxidase, however no effect was noticed in the activities of acid and alkaline phosphatases, melanin deposition and the contents of nucleic acids in the skin of rats. The intensity of staining reaction for sulfhydryl groups appeared markedly increased due to the proliferation of the hair follicles in the painted skin. The absence of any effect on the cutaneous melanin appears of significance since manganese has been found to reduce neuromelanin in rhesus monkeys. The implications of these findings are discussed.

Ultrastructural morphometric examinations show that the normal rat myocardium of the left ventricle contains about 15% interstitial connective tissue, half of which (53%) is composed of extracellular space, ground-substance and collagen, 41% of blood capillaries and 6% of interstitial cells. These percentages vary in the course of swimming training for periods of 45, 180 and 360 hours in dependence on the duration of training and load. The volume ratio of the interstitium increases after 45 hours of exercise from 15 to 17 %, after 180 hours of training to 19% and after 360 hours of training to 22%. Relative changes in morphometric parameters (volume and surface density, number per unit area) of the interstitial components are observed in relation to untrained animals. Owing to a shift in the volume ratio of interstitium to muscle cells in favour of the interstitium, the real volume ratio changes only in the case of extracellular space and capillaries.

After 45 hours of training the volume ratio of extracellular space to interstitium decreases to 50%, that of the capillaries increases to 44%. After 180 hours of training the volume ratio of blood capillaries diminishes to 32%, while that of extracellular space increases (62.5%). This ratio remains constant in the course of further training even if the load is increased. Exercise has virtually no bearing on the volume ratio of connective tissue cells.

There is an increase in the capillary density of the myocardium and a reduction in the extracellular space after 45 hours of training. After 180 hours of maintenance training the ratio is inversed again and after that is no longer influenced by exercise.

Unlike the number per unit area, the surface density of the capillaries increases with increasing intensity of the swimming load throughout the training period. The volume ratio of capillary to muscle cells changes in favour of the capillaries in the course of training. Specific surface density of the capillaries increases continuously up to a training period of 180 hours, and there is no further increase even if training is continued after that. The morphometrical changes in the capillaries suggest that a short, but intensive period of training brings about an increase in the capillary surface, which can be maintained but not increased through further training.

The activity of the ZnTP (Felicetti und Rath 1975; Rath and Felicetti 1975) was investigated histo- and biochemically in neurinomas of trigeminal nerves of rats. The tumors were induced by a single transplacental pulse of 30 mg ENU/kg on the 17th day of gestation. The rats were killed at the age of 40 to 160 days. The activity of the ZnTP is demonstrated histochemically by a coupling azo dye technique with 1-naphthylphosphate after Rath and Felicetti (1975) as well as a lead nitrate method with 4-nitrophenyl phosphate at the age of 40 to 140 days. Biochemical investigations of the trigeminal nerves are performed at the age of 140 and 160 days only. The separation of ZnTP is carried out by isoelectrofocusing in polyacrylamide gels after Felicetti and Rath (1975).

Together 14 neurinomas are found in the trigeminal nerves of 53 rats. All neurinomas show a high activity of the ZnTP. The ZnTP activity is absent in normal Schwann cells. Three trigeminal nerves of rats subjected to the transplacental pulse of ENU harbour small foci of ZnTP activity without detectable neoplastic cell proliferation. Similar spots of enhanced ZnTP activity have never been found in control rats. This rises suspicion that the neoplastic proliferation of cells is preceded by the activation of ZnTP.

Supernatants (105,000 g) prepared from extracts of liver and kidney were injected at different concentrations into 10 day-old rats and the resulting effects on ³H-thymidine incorporation in liver, kidney and lung were measured over a period of 24 hours. Incorporation in all three organs is inhibited by supernatants from both liver and kidney, with maximal activity between 12 and 18 hours after injection. Fractions prepared from liver supernatant by ultrafiltration and alcohol precipitation also showed no specific effect on liver cells. In order to test whether the activity of any factors in the supernatants is cell-cycle dependent, organs of baby rats were synchronized by two different procedures: a) injection of a 3.5% casein solution, b) injection of hydroxyurea (2×10 mg/kg body weight with an interval of one hour).

Inhibitory effects were only observed when the supernatants were injected during the G1-phase of the target cells. Supernatants prepared in a similar way from other organs such as spleen, lung or heart also inhibited thymidine incorporation in casein-stimulated liver from baby rats. All of our investigations have therefore failed to find any indication of tissue-specific activity in these extracts.

Liver absorbed rabbit anticanine brain serum (ABS) was tested for its immunosuppressive capacities in dogs. Single intravenous injection of ABS led to significant decrease in lymphocyte counts and functions after 24 hours, as measured by phytohemagglutinin stimulation and mixed lymphocyte culture. The immunosuppressive effectiveness of ABS could further be documented by prolongation of skin graft survival in unrelated dogs which were treated daily for 12 days with intramuscular ABS injections. The ABS was generally welltolerated. One dog died of pneumonia. All dogs showed moderate decrease in platelet counts after 10 days of ABS treatment. Autopsies showed normal cerebral histology, moderate lymphoid hypoplasia, and no changes in the bone marrow and liver. The results suggest that liver absorbed anti-canine brain serum is a potent immunosuppressant with limited toxicity.

The carcinogenic effect of N-bis(2-hydroxypropyl)nitrosamine (BHP) was studied in newborn Wistar rats. Tumors were induced in the lung (adenoma), pancreas (adenoma), kidney (nephroblastoma), and ovary (benign granulosa cell tumor) at 24 weeks after the treatment and in the lung (adenoma and adenocarcinoma), liver (hemangioma, hemangioendothelioma, and hepatocellular carcinoma), pancreas (adenoma), kidney (renal cell carcinoma and nephroblastoma), thyroid (adenocarcinoma) and ovary (benign and malignant granulosa cell tumors) at 52 weeks. The highest incidence of tumor was seen in the liver of rats applied BHP within 24 hours after birth.

These results indicate that newborn Wistar rats are more susceptible to BHP than are adult rats.