Springer Science and Business Media LLC

All mice partially deuterated by ingestion of 29% heavy water for 12 days survived whole body gamma irradiation (8.5 Gy) from a60Co source, whereas 42% of nondeuterated control animals died from bone marrow failure. The incorporation of3HTdR into enterocytic DNA, as measured by autoradiography and liquid scintillation spectrometry, was used to assess the proliferative activity of small intestinal epithelium. The sequence and the magnitude of changes in tritium activity were in good agreement. Deuteration alone resulted in a reduced proliferative activity of small intestinal crypt epithelium, particularly in the basal cell positions and the first positions of the proliferation compartment. The number of positions occupied by the proliferative compartment and the crypt length were, however, barely affected by deuteration. The radiation-induced depression of DNA synthesis in the proliferative compartment was of similar magnitude in both groups. Crypt epithelium in deuterated mice, however, displayed signs of an accelerated and/or enhanced regeneration. The cytokinetic changes in deuterated animals are consistent with a protective effect for clonogenic intestinal epithelium at the time of irradiation.

Groups of mice were inoculated with strains ofToxoplasma gondii of either high or low virulence strains. The response of the lymph nodes, spleen and thymus was studied histologically and antibodies were assessed by the dye-test technique. The low-virulence strain induced changes in all three organs indicative of an immunological response, both in respect of cellular and humoral immunity. The high-virulence strain produced rapid lymphoid depletion in lymph nodes, spleen and thymus with areas of necrosis. It is suggested that the high-virulence strain has a toxic effect on the Reticulo-Endothelial system allowing unrestricted proliferation of the organism with eventual death.

Effects of anoxemic cell injury on rat pancreatic acinar cells were studied in a preparation where tissue samples were incubated at temperature between 18–20° C in a moist atmosphere for 0, 0.5, 1, 3, 6, 12, and 24 h in vitro. Electron microscopy revealed that disintegration of acinar cells began by swelling of various cell compartments and gradual breakdown of cell membranes. Zymogen granules remained morphologically intact for at least 3 h. There were no signs of increased autophagic activity during the period of observation. Myelin figures and other membranous remnants of disintegrated cells, together with individual cells and cell organelles whose morphology was relatively well preserved were seen even after 24 h incubation. The secretory response of acinar cells to pancreozymin stimulation, as measured by amylase release into the incubation medium in vitro, decreased progressively closer to zero during 12 h autolysis. No active trypsin could be detected in the tissue samples during the 24 h observation time. It was concluded that during hypoxic autolysis at room temperature between 18–20° C in vitro:

Highly sulfated glycosaminoglycans (GAG) or proteoglycans (PG), especially heparan sulfate (HS) and heparan sulfate proteoglycan (HSPG), are considered to be intimately associated with amyloid deposits in different types of amyloidosis. Based on this relationship an important role for HS has been suggested in amyloidogenesis. The present immunohistological and ultrastructural study shows that in bovine renal AAamyloidosis, sulfated GAG/PG was not restricted to amyloid deposits proper and that areas without GAP/ PG were also present within the amyloid. Both glomerular and papillary amyloid contained HS (PG), and the latter also contained chondroitin sulfate (CS) and dermatan sulfate (DS), suggesting a correlation between the location of the amyloid and the type of GAG/PG deposited. Amyloid P component (AP) had a distribution similar to that of HSPG, confirming their affinity-based relationship. The GAG types found ultrastructurally in amyloid fibril preparations of glomerular and papillary amyloid isolated from the same kidney, reflected the immunohistological findings. HS was shown to be the predominant GAG in all papillary amyloid fibril extracts. Taking into account the chemico-physical properties of HS, it cannot be excluded that this predominance is introduced by the purification procedure. These results suggest that the association of GAG/PG and amyloid is not necessarily mutually obligatory and that the proposed importance of GAG in amyloidogenesis is disputable.

Daily oral administration of 20 or 60 mg/kg chlorphentermine for 1 week produced a dose-related increase in the number of myeloid bodies in renal tissue of both adult and newborn rats. In adults myeloid bodies were present throughout the kidney while in neonates these bodies were found predominantly in the medullary region. Simultaneous administration of phenobarbital and either chlorphentermine dose resulted in a reduction in the number of myeloid bodies in kidneys of adults and newborns. Our data show that phenobarbital prevented the chlorphentermine-induced lipidosis in renal tissue and that newborns appear less sensitive than adults to the histopathologic action of anorectic on kidney.

Seven daily intramuscular (im) injections of cortisone acetate (25 mg/Kg b.w.) given to rats or rabbits produced, (i) a pronounced reduction in the numbers of small lymphocytes in thymus-independent areas, (ii) atrophy of the thymic cortex, (iii) atrophy of germinal centres and (iv) a consequent depressed production of germinal centre-derived cells. Lymphocyte depletion was not caused by cell lysis. Moreover cell traffic between peripheral lymphoid organs did not seem to be altered. A revival of the depressed germinal centres in cortisone-treated (inbred) rats could be achieved by a transfer of bone-marrow cell suspensions from normal, cortisone-treated or T-cell-deprived animals. It was concluded that cortisone acetate arrests the migration of B-lymphocytes from the bone marrow to germinal centres in peripheral lymphoid organs, and that the accumulations of lymphoid cells in the bone marrow of cortison-treated animals might be composed of immature or mature T- and B-lymphocytes.

The processes of polyploidization in normal human liver parenchyma from 155 individuals aged between 1 day and 92 years were investigated by Feulgen-DNA cytophotometry. It was shown that polyploid hepatocytes appear in individuals from 1 to 5 years old. Up to the age of 50 years the accumulation rate of binucleate and polyploid cells is very slow, but subsequently hepatocyte polyploidization is intensified, and in patients aged 86–92 years the relative number of cells with polyploid nuclei is about 27%. Only a few hepatocytes in the normal human liver reach 16C and 8C×2 ploidy levels for mononucleate and binucleate cells respectively. Using a mathematical modeling method, it was shown that during postnatal liver growth the polyploidization process in human liver is similar to that in the rat, and that polyploid cells are formed mainly from binucleate cells. As in rats, prior to an increase in ploidy level, diploid human hepatocytes can pass several times through the usual mitotic cycles maintaining their initial ploidy level. After birth, only one in ten hepatocytes starting DNA synthesis enters the polyploidization process. At maturity about 60% of 2C-hepatocytes starting DNA synthesis divide by conventional mitosis, the rest dividing by acytokinetic mitosis leading to the formation of binucleate cells. During ageing the probability of hepatocyte polyploidization increases and in this period there are two polyploid or binucleate cells for every diploid dividing by conventional mitosis.

The ultrastructural morphology of mast cells localized in rat mesenteries was studied after intraperitoneal implantation of L 5222 rat leukemia cells in syngeneic and allogenic hosts. It became evident that the mast cells in the syngeneic (BDIX rat) as well as the allogeneic system (BN rat) showed nor morphological alterations. Degranulation was never observed. This is in contrast to the behavior of macrophages which displayed a strong phagocytotic activity in allogeneic hosts. Thus, it seems that mast cells, under the present experimental conditions, remained inactive during a phase of intense tumor rejection.

This study has been undertaken in order to compare in detail cell proliferation in the mucosal crypts at several sites along the length of the large bowel of the rat. The techniques which have been used include simple morphometry, calculation of mitotic and tritiated thymidine labelling indices, metaphase arrest with vincristine, and the fraction of labelled mitoses method. Major differences exist in the size and shape of the crypts at different sites. In particular the distribution of the proliferating cells within the crypt varies. Mean cell cycle time ranges from 58 h in the descending colon to 25 h in the caecum; this variation appears to be brought about largely by changes in the duration of G1, the other phase durations remaining relatively constant. There is also variation in cell cycle time and growth fraction at different levels within the crypt; throughout the bowel cells appear to cycle more slowly at the bottom of the crypt, but changes in growth fraction do not display a similarly consistent pattern. Clearly the organisation of cell proliferation in the normal rat colon is very complex, and strict definition of anatomical location is required in any study of cell proliferation whether in normal or in diseased animals.

To clarify interactions between carcinoma and mesenchymal cells, we examined the extracellular matrix-substance remaining on culture dishes after confluent growths of gastric carcinoma cells were removed with EDTA. The matrix synthesized by poorly differentiated adenocarcinoma cells (cell lines KATO-III and MKN-45) cultivated in serum-free medium has a fibroblast (cell line WI38)-attachment activity, which is not detected in the matrix synthesized by a well differentiated adenocarcinoma (cell line MKN-28). This activity was not observed in KATO-III-matrix extracted with 6 M urea, but could be detected in a 1% SDS extract from the remaining matrix on the culture dishes after 6 M urea extraction. The activity was abolished by treatment with pronase (16(μg/ml), trypsin (0.005%) or alkali, but was unaffected by collagenase (80 μg/ml, 4 h) or chondroitinase ABC (1 U/ml, 1 h). It is conceivable that the fibroblastattachment activity of the matrix produced by poorly differentiated adenocarcinoma cells is related to the proliferation of interstitial connective tissue in vivo.