Bone Marrow Blood Vessels Research Articles

Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions

More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible. Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 x 10(7) LNCaP prostate cancer cells or phosphate-buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2, 4, 6, and 8 weeks after injection. LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete. The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.

Pulmonary vascular sclerosis in an albino rat with leukemia

The animal investigated was a two years old male control Sprague-Dawley rat which died spontaneously during a carcinogenicity study. Post-mortem examination disclosed hepatic and splenic enlargement. At microscopical examination, massive leucaemic infiltration was observed in many tissues/organs, including bone marrow, spleen, liver and renal blood vessels. A very unusual finding was observed in the lung, consisting of scattered micronodules which replaced most of the lung parenchyma. They contained collagen, displaying a somewhat circular distribution at the periphery of the lesions, fibrin, leukemic cells and fibroblasts. Immunostaining for desmin revealed the presence of smooth muscle fibers within the nodules, while staining for elastic fibers showed clearly that the internal and external elastic membranes were identifiable within the nodules. The diagnosis of pulmonary vascular sclerosis was made on the basis of microscopical and immunohistochemical findings.

Development of Leucocytozoon ziemanni (Laveran)

Development of Leucocytozoon ziemanni ( = L. danilewskyi) was studied in its simuliid vectors and in saw-whet owls, Aegolius acadica. Sporogony was completed in Simulium aureum, S. latipes, and Prosimulium decemarticulatum within 5 to 7 days at 21 C after gametocytes were ingested. Sporozoites were inoculated into 4 owls and hepatic biopsies were performed at intervals thereafter. Four types of schizonts were observed: (a) hepatic forms in parenchymal cells, (b) renal forms in tubular cells, (c) megaloschizonts in endothelial cells lining the walls of blood vessels in spleen, liver, kidney, heart, intestine, gonad, and bone marrow, and (d) small, wormlike schizonts in endothelial cells of the lung. None was observed in the brain. Sporozoites developed in hepatic parenchymal and renal tubular cells. Following completion of primary schizogony in 4 days, merozoites penetrated polychromatic erythrocytes and matured about 2 days after as round gametocytes. Megaloschizonts were seen from 5 days and matured 3 days onwards. Appearance of elongating gametocytes from 8 days postinjection coincided with the rupture of the megaloschizonts. Merozoites from the latter developed in erythroblasts and lymphocytes and matured about 2 days later as fusiform gametocytes. The life cycle shows similarities to that of L. simondi with the sequential appearance of hepatic and megaloschizonts and the associated round and fusiform gametocytes. Gametocytes of species of Leucocytozoon have been reported from owls from different regions of the world: in Europe by Danilewsky (1889, 1890), Ziemann (1898), Laveran (1902, 1903), Berestnev (1904), Cardamatis (1911), Franca (1912), Moldovan (1913), and Franchini (1923); in Asia by Ogawa (1911); in Africa by Kerandel (1913), Leger and Leger (1914), Fantham (1926), and Gaud and Petitot (1945); in the Americas by Carini (1920), Coatney and Roudabush (1937), Bennett and Fallis (1960), and Khan and Fallis (1970a); and in Australia by MacKerras and MacKerras (1960). Round and fusiform gametocytes have been observed but whether they arise from different schizogonic cycles as in L. simondi (Desser, 1967; Yang et al., 1971) is unknown. Observations pertaining to this follow. MATERIALS AND METHODS Six adult, saw-whet owls, Aegolius acadica, trapped at Toronto Island in October 1967, were held over winter in an animal house in Toronto. Examination of centrifuged as well as regular blood smears from these owls (once or twice weekly) over an 8-month period revealed no paraReceived for publication 14 June 1973. * This study was done during the author's tenure as a postgraduate student at the University of Toronto. Support from the Medical Research Council of Canada Grant M2998 to Dr. A. M. Fallis, Professor Emeritus and Special Lecturer, Department of Parasitology, School of Hygiene, University of Toronto, is gratefully acknowledged. sites in 4 birds while the 2 others harbored chronic infections of L. ziemanni (status of this species to be discussed by Bennett, Laird, Khan, and Herman, in litt. ). In the spring of 1968 the owls were taken to the field station at Algonquin Park, Ontario, where they were subsequently held in cages in an animal house. Wild-caught simuliids were used in these experiments. They were collected from late May 1968, in the manner described by Bennett (1960), after feeding on the 2 naturally infected owls, and were subsequently retained in containers at about 21 C (Khan and Fallis, 1970b). Unfed flies collected at the same time served as controls; none of 22 was infected. Engorged flies were dissected daily to follow the sporogonic development. Midguts and salivary glands were dissected and spread thinly prior to fixation with methanol and staining with Giemsa. To determine the time of appearance of the gametocytes and the pattern of schizogony, 4 owls were experimentally infected with sporozoites. The methods of preparation and inoculation of the latter have been reported previously (Khan and Fallis, 1970b). Blood smears were prepared daily from all birds following injection. Biopsies were performed at intervals thereafter and the birds were necropsied subsequently. Blood smears and tissue imprints were air-dried before fixing with methanol and staining with Giemsa. Tissues were fixed in Carnoy's and sections, cut at 4 ,u, were stained by the Giemsa-Colophonium method. Photomicrographs were made with a Zeiss photomicroscope. Measurements are in microns.

Studies on the Organ Structure of Bone Marrow, with Special Reference to the Fine Structure of Its Vascular System

The structure of bone marrow, especially the relation between its vascular system and myeloid cells, has been studied in femora of rabbits mainly by an injection method with India ink and by the silver-impregnation method of SUZUKI. The results of the investigation are as follows:1. Walls of the blood-sinusoids in bone marrow are lined by delicate cytoplasmic membrane composed of littoral cell-like endothelial cells, whose cytoplasm shows net-like pattern in relief with meshes of different shapes and sizes. The spaces in these meshes are generally shut up with extremely thin cytoplasmic membranes, but in some spots they remain open to show small pores through which matured erythrocytes could pass.2. By the modes of ramification the blood-sinusoids in bone marrow can be classified into two types: the first net-like type occupies the spaces between osseal trabeculae near the epiphysial plate and is connected by blood capillaries with arterioles, and the second straight type comming out of the former lies in meta- and diaphysial part of bone marrow.3. Two different types of arterio-venous communication are found in bone marrow: the one is connected by capillaries, another communicate through the arteriovenous anastomosis. The anastomosis combines arterioles with venules in the subcortical part of bone marrow, while capillaries convey the blood from arterioles into blood-sinusoids of the first type near epiphysial line.4. In bone marrow of the spongial and diaphysial parts of bone, there often occur blood-capillaries with blind ends at which figures of angioblast or endothelium in degeneration or regeneration can be observed.5. It is very important that many small pores communicating the blood-stream with perivascular spaces of bone marrow can be observed in the cytoplasms of endothelial cells lining the small arteries. The calibers of these pores are so small that a single erythrocyte can not pass through them except blood-plasma. This sort of perforation of the wall of small artery seems to cause the elevation of fluid-pressure in the perivascular spaces wihtin bone marrow.6. On the section stained with Azan-staining the cytoplasm of the endothelium of the blood-sinusoid appears blue in color as these of normoblast before the enuclation stage. These data suggest that the cytoplasms of the endothelium of the blood-sinusoid and of the normoblast may have the same densities in structure.7. According to MATSUSHITA the cytoplasm of the normoblast, youngest erythrocyte, becomes much rigid in structure, forming elastic cytoplasmic membrane in its surface, immediately after the enuclation, and stained green to orange in color by Azan-staining. These data and the peculiar structure of the blood-vessels in bone marrow make it possible to interprete the mechanism by which only matured erythrocytes come into the peripheral blood-stream. In other words, the rigidity of the matured erythrocyte may overcome the softness of the delicate cytoplasmic membrane of the blood-sinusoid and it passes through the membrane or the pores into the peripheral blood-stream.