L.C.J. Yong

Streptozotocin induced diabetic nephropathy and renal tumors in the rat

Adult Wistar rats rendered diabetic by a single dose of streptozotocin develop renal morphological changes which show subtle differences compared to those seen in human diabetic renal disease. The early tubular degeneration is sited in the distal rather than the proximal convoluted tubule and subsequent glomerular lesion shows linear deposits of IgG and albumin in the basement membrane rather than in the mesangium. The carcinogenicity of streptozotocin in the rat is reconfirmed.

The mast cell: III. Distribution and maturation in various organs of the young rat

The changing population-density of mast cells in various organs was plotted for rats aged 1/2 to 90 days and correlated with histochemical studies on the stage of maturation of cells. Mast cells are present at birth in liver and spleen and are particularly associated with foci of haemopoiesis. In bone marrow mast cells are absent at birth but become progressively more numerous with increasing age of the animal. The association of mast cells firstly with foci of extramedullary haemopoiesis and secondly with medullary foci coupled with their detection in peripheral blood strongly suggests that mastopoiesis may be analogous with granulopoiesis. In thymus mast cells are usually associated with interlobular connective tissue stroma, but in the parenchyma they are found toward the medullary side of the cortico-medullary junction. Such a distribution suggests the possible origin of mast cells from lymphocyte or thymocyte. In other tissues examined mast cells are frequently associated with connective tissue stroma and blood vessels.

The mast cell: distribution and maturation in the rat.

This paper reports preliminary studies in the rat of the connective tissue mast cell — its origin, distribution in various tissues, regeneration and function, as well as its relationship with basophil leucocytes and ‘mucosal mast cells’. Connective tissue mast cells and basophil leucocytes exhibit a reciprocity of incidence in animals such as the rat and rabbit, and with mucosal mast cells comprise a family of cells that share the common feature of having a cytoplasm packed with granules that stain metachromatically. At least in connective tissue mast cells, these granules represent miniature pharmacological storehouses.The relative insolubility in aqueous solutions of the granules of connective tissue mast cells in the rat has made this species a popular one for laboratory investigations of the mast cell. Progressive sulphation of the granules of rat mast cells is demonstrable by staining with Alcian blue and safranin. Coupled with morphological features, such staining permits the identification of four stages in the maturation of mast cells. The maturation and distribution of these cells is illustrated for mesentery, omentum and peritoneal fluid. Although it has long been accepted that mast cells are particularly associated with the blood vessels of the vascular arcades of the mesentery, our own work inneonatal rats has indicated clearly that the association is with lymphatic rather than blood vessels. However, this association with lymphatic vessels seems restricted to the mesentery and omentum.In further work in the newborn rat, mast cells have been observed in substantial numbers inskin andthymus, the population of mast cells in these organs being maintained during the next 3 months. In theliver andspleen of the newborn rat, mast cells are reasonably numerous in the foci of haemopoiesis, but progressively decline in number during the initial 4 weeks, in step with the disappearance of extramedullary haemopoiesis. On the other hand, thebone marrow becomes populated by mast cells, particularly during the 2nd and 3rd weeks of life. In theconnective tissue ofheart, lung, stomach andportal tract of the rat, mast cells are practically absent at birth but progressively increase in number during the initial postnatal month. Thereafter, their number remains fairly steady.The presence at birth of mast cells in extramedullary and subsequently in medullary foci of haemopoiesis, suggests that the process of mastopoiesis may be analogous to that of granulopoiesis in haemopoietic tissues. This possibility is discussed in relation to other evidence concerning the origin of mast cells.

Association of mastopoiesis with haemopoietic tissues in the neonatal rat.

Mast cells in the newborn rat occur in haemopoietic foci of liver and spleen, but disappear from those foci as extramedullary haemopoiesis ceases during the initial postnatal month. At the same time, mast cells increasingly populate bone marrow and connective tissues of heart, lung, stomach and portal tract of liver.

The mast cell: II. distribution and maturation in the peritoneal cavity of the young rat

Summary In rats aged 1/2 to 60 days, the development of the mesentery and omentum involves a substantial modification of the initial lymphatic supply of these membranes and the postnatal development of the ‘milk spots’ of the omentum. In both membranes, mast cells are scarce at birth but progressively increase in number and maturation with increasing age of the rat. In the paravascular zones of the mesentery, mast cells are particularly associated with lymphatic vessels, rather than with blood vessels. Mast cells are also scarce at birth in the free peritoneal fluid, but increase progressively in number with increasing age of the rat. The initial population consists of about 90% stage 1 cells and 10% stage 2. Progressive maturation results in successive waves of stage 2 cells during the 2nd week, of stage 3 cells during the 2nd and 3rd weeks, and of stage 4 cells during the 3rd and 4th weeks. These and other results are interpreted to indicate that mast cells in free peritoneal fluid probably arise from free precursor cells rather than by migration from the peritoneal membranes.

A comparative study of cultured vascular and lymphatic endothelium

There is comparatively little knowledge of the structure and function of cultured lymphatic endothelium. A study was carried out to compare the intrinsic growth characteristics of cultured lymphatic endothelial cells with cultured endothelial derived from blood vessels. It was found that cultured lymphatic endothelium has growth requirements and growth characteristics similar to vascular endothelium. It also possesses FVIIIRA and Weibel-Palade bodies for specific identification. The results of this study have provided important base line data for subsequent studies of the pathobiology of lymphatic endothelium.

A combined histochemical and autoradiographic study of the distribution and maturation of peritoneal mast cells in the rat

The relationship of mitotic activity and degree of cytological differentiation for mast cells of the peritoneal cavity of the rat was studied using combined autoradiographic and histochemical techniques. A mitotic pool of mast cells can be differentiated from a non-mitotic pool, the former containing cells with immature cytoplasmic differentiation and the latter with fully developed cytoplasmic histochemical properties.

The effect of oxygen toxicity and cigarette smoking on the binding of heterologous antibodies to alveolar basement membrane in the rat.

It has been suspected that pulmonary lesions of the Goodpasture type may be the result of circulating antibodies to alveolar basement membrane and that environmental factors such as cigarette smoke may influence antibody binding. Carefully designed experiments in this study have shown that exposure to cigarette smoke for 3 weeks or 100% oxygen for 65 h did not influence the binding of heterologous antibodies to alveolar basement membrane in Wistar rats, nor did these regimes increase any pathological changes associated with the antibody binding as detected by light microscopy. The results which are at variance with other reported findings are discussed with reference to reported animal models of antibody mediated pneumonitis and Goodpastures syndrome in man.

Pathological changes in the heterologous phase of antibasement membrane antibody mediated disease in the rat

The immunological and structural changes during the heterologous phase of experimental antibasement membrane antibody mediated disease was sequentially studied in the rat following single i.v. injections of rabbit antibodies to basement membrane antigens prepared from kidney, lung and salivary gland tissues. Although each of the anti-bodies bound strongly to GBM, structural changes were initially subtle accompanied by proteinuria and hematuria. More severe structural changes related to dose and duration of the disease did not appear for several weeks.

A MODEL OF BILE DUCT HYPERPLASIA IN THE RAT INDUCED BY DIETHYLNITROSAMINE AND SELECTIVE CYTOTOXICITY

&NA; Adult Wistar rats were subjected to a chemical carcinogenesis regimen involving initiation with diethylnitrosamine (DEN) and cytotoxic selection of initiated cells following partial hepatectomy. The livers of treated rats exhibited sequential changes of vacuolar degeneration and hepatocellular nodular hyperplasia up to 5 mth after completion of the experimental regimen. The hyperplastic nodules regressed slowly at that time. Cystic bile duct hyperplasia emerged with high frequency between 5 and 15 mth after completion of the regimen. The nitrosamine‐initiated nodular and biliary hyperplasias could not be unequivocally accepted as preneoplastic lesions since frankly neoplastic transformation under these conditions was a relatively rare occurrence.