Effect of circumstances and/or organs on the grade of cancer growth and malignancy

The effect of circumstances and/or organs on the grade of cancer growth and malignancy was studied, using hereditarily identical VX2 cancer. VX2 cancer cells, 10(6) cells/0.1 approximately 0.2 ml, were injected into the liver, portal vein, stomach- and colon-walls of Japanese white rabbits. Each of the experimental groups consisted of 14, 12, 19 and 24 animals, and 3 or 4 animals of each groups were sacrificed 7, 14, 21 and 28 days after the implantation. All the animals of portal vein and liver groups died of cancer within 3 and 4 weeks respectively. However, all the animals of stomach and colon groups survived during 4 weeks. Although cancer volume doubling time was not calculated in portal group because of the multiple and diffuse tumor-formation, the time was 2.6 days in liver, 4.3 days in colon and 5.9 days in stomach groups in which a single tumor developed. Lymphatic and/or hematogenous metastases were found at the same time after the implantation as vascular invasion occurred. Metastases were confirmed in 100% in liver group and 40% in portal group 2 weeks after the implantation, and 80% and 50% in colon and stomach groups respectively 4 weeks after the implantation. The results suggested that hereditarily identical VX2 cancer was variable in the different organs and circumstances, and that the growing circumstances strongly affected the cancer malignancy. It was also suggested that the malignancy was correlated with the growth rate and the time of metastasis of cancer.     

A clinicopathological study of prognostic factors in esophageal cancer

To evaluate the malignancy of esophageal cancer, we made a statistical clinicopathological study on 66 patients resected with definite operative and histological findings. The cumulative 5-year survival rate was 26.1%. By Cox's proportional hazard model depth and lymph node metastases were the prognostic factors in "Guide Lines for the Clinical and Pathological Studies on Carcinoma of the Esophagus". New histological factors for quantity idea: 1) depth judged by presence of cancer cells before irradiation; 2) intramural spreading characteristics; 3) volume of tumor measuring the infiltrating area of each layer; 4) distribution of metastatic lymph nodes set up by anatomical restriction and surgical risk; 5) number of metastatic lymph nodes. By analyzing the interaction of these 5 factors, the depth was correlated with the volume and the intramural spreading characteristics. The lymph node metastases were correlated significantly with the volume but not with the depth. The depth and the distribution of metastatic lymph nodes influenced prognosis according to Cox's proportional hazard model. Estimated survival rates of these factors were fitted to actual survival rates respectively. Postsurgical survival and adjuvant therapy may be determined by histological factor analysis.     

Ia-expressing microglial cells in experimental allergic encephalomyelitis in rats

Summary Monoclonal antibodies (MRC OX-6 and OX-17) recognized three types of cells expressing Ia antigen during the course of acute experimental allergic encephalomyelitis (EAE) in rats. In earlier stages of the disease, in animals with or without paralysis, Ia antigens were mostly localized to subarachnoidal and perivascular lymphocytic and histiocytic cell infiltrates, possibly serving as antigen-presenting cells. On the other hand, in convalescent rats, Ia antigens were expressed in a large number of cells with dendritic processes heavily populating the spinal gray matter. The appearance of these Ia-expressing cells in the convalescent stage coincided with the development of degenerating axon terminals in the spinal gray matter. These Ia-expressing cells possessed morphological features characteristic of microglia and were positive for ML-1 lectin but did not express glial fibrillary acidic protein. Immune electron microscopy disclosed the presence of Ia reaction products in the Golgi apparatus, endoplasmic reticulum and plasma membrane of these cells with dendritic processes, indicating active synthesis of Ia molecules in microglia. In addition, Ia antigens were localized to the cells with ultrastructural features of macrophages. Thus, Ia-expressing cells in EAE seems to play dual roles: the induction of immunological reactions during earlier stages and the participation in reparative processes during convalescence.Supported by Grants-in-aid from the Ministry of Health and Welfare for Intractable Neuroimmunological Diseases and from the Ministry of Education, Science and Culture (Project 61570380 to HK)     

Evidence for a role of basal ganglia in the regulation of rapid eye movement sleep by electrical and chemical stimulation for the pedunculopontine tegmental nucleus and the substantia nigra pars reticulata in decerebrate cats

The present study was to determine how afferents from the substantia nigra pars reticulata (SNr) of the basal ganglia to the pedunculopontine tegmental nucleus (PPN) in the brainstem could contribute to the control of behavioral states. We used anesthetized and acutely decerebrated cats (n=22). Repetitive electrical stimulation (10-100 Hz, 20-50 microA, for 4-20 s) to the ventrolateral part of the PPN produced rapid eye movement (REM) associated with a suppression of postural muscle tone (REM with atonia). Although repetitive electrical stimuli (10-200 Hz, 10-60 microA, for 5-20 s) delivered to the dorsolateral part of the SNr did not evoke eye movements or muscular tonus in baseline conditions, it altered the PPN-induced REM with atonia. The following three types of effects were induced: (1) attenuation of the REM with atonia; (2) attenuation of muscular atonia without changes in REM (REM without atonia); and (3) attenuation of only REM. The optimal stimulus sites for these effects were intermingled within the lateral part of the SNr. The PPN-induced REM with atonia was abolished by an injection into the PPN of muscimol (1-15 mM, 0.1-0.25 microl), a GABAA receptor agonist, but not altered by an injection of baclofen (1-10 mM, 0.1-0.25 microl), a GABAB receptor agonist. Moreover, an injection of bicuculline (1-15 mM, 0.1-0.25 microl), a GABAA receptor antagonist, into the PPN, resulted in REM with atonia. On the other hand, an injection of muscimol into the dorsolateral part of the SNr (1-15 mM, 0.1-0.25 microl) induced REM with atonia, which was in turn eliminated by a further injection of muscimol into the PPN (5-10 mM, 0.2-0.25 microl). These results suggest that a GABAergic projection from the SNr to the PPN could be involved in the control of REM with atonia, signs which indicate REM sleep. An excessive GABAergic output from the basal ganglia to the PPN in parkinsonian patients may induce sleep disturbances, including a reduction of REM sleep periods and REM sleep behavioral disorders (REM without atonia).     

Genesis of pulmonary foam cells in rats with diet-induced hyper beta-lipoproteinaemia

Hyper beta-lipoproteinaemia in rats was produced by feeding a standard diet to which was added excess cholesterol and cholic acid, with or without olive oil, for 4, 8, and 12 weeks. The beta-lipoprotein percentage in serum lipoprotein electrophoresis and lipid contents in very low density lipoprotein and low density lipoprotein fractions in these rats were significantly higher than in the control rats fed the standard diet only. The percentage of foamy monocytes (FMs) to the total number of blood monocytes (BMs) from mononuclear leucocyte fractions and percentage of pulmonary foam cells (PFCs) to the number of alveolar macrophages (AMs) from bronchopulmonary lavage fluids in the rats increased with the extension of the feeding period and were significantly higher than those in the controls. An increase in the percentage of PFCs was closely correlated with that of FMs in the rats. FMs and PFCs had cytoplasmic fine vacuoles proved to be neutral lipid and cholesterol. Histologically, PFCs made an appearance in the lungs of all the rats as early as 4 weeks after the start of feeding. The degree of the PFCs' development increased as the feeding period lengthened. When latex particles were injected intravenously into rats at feeding week 4, the percentage of latex-ingested AMs to the number of AMs in the rats was significantly higher than that of the controls at 4 and 8 days post-injection. The percentage of latex-ingested PFCs to the number of latex-ingested AMs increased with the lapse of a day after injection and was significantly higher than that of the controls at 2, 4, and 8 days post-injection. The present findings suggest that the foamy transformation of BMs and their migration into the pulmonary alveoli may be a potential mechanism of the PFCs' development in rats with hyper beta-lipoproteinaemia.