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Neutrophils and spleens were prepared from mice after treatment to induce amyloid deposition. The deposition of amyloid was accelerated in normal recipients by intravenous injection of more than 2 x 10(4) neutrophils, and intraperitoneal injection of supernatants obtained by homogenization and centrifugation of the neutrophils and spleens. The supernatants were subjected individually to DEAE ion-exchange chromatography. Amyloid enhancing factor (AEF) activity was present in peaks eluted at an NaCl concentration of 0.17 M. The fractions containing AEF were subjected to high-performance liquid chromatography (HPLC), and AEF was eluted at a position corresponding to about 15 KDa. Purified AEF was analyzed by amino acid sequencing and gas chromatography. The N-terminal amino acid was blocked, and AEF contained some saccharides including glucose, mannose, galactosamine and sialic acid, and an undefined substance (probably derived from certain proteins). Immunoelectron microscopy by the pre-embedding method using an anti-AEF antiserum demonstrated that the cytosol, but not primary and specific granules in neutrophils from the spleen of amyloid-laden mice, reacted with the antiserum. These findings suggest that AEF is a glycoprotein associated with neutrophils.

White male rabbits, weighing about 3 kg, were injected intravenously with 5 ml of 0.1% saponin solution dissolved in physiological saline once a week for six months. The sequential histological changes in the kidneys were observed by repeated biopsies and, in addition, the animals were subjected to necropsy for light and electron microscopic examinations. Amyloid protein was purified from the animal tissues, estimated at approximately 6,300 daltons in molecular weight by SDS-PAGE and considered as an AA type protein based on its amino acid sequence study. The antibody against the purified amyloid protein was produced in guinea pigs and was used for immunohistochemical studies. The deposition of amyloid started initially in mesangial matrices and subendothelial regions of the glomeruli, but at the end the spleen, kidney and bowels were found to be frequent sites of deposition. The amyloid deposited in the tissues was specifically positive by the indirect immunohistochemistry using the prepared antibody. This antibody also reacted positively to human materials with secondary amyloidosis. These results indicate that amyloidosis induced by saponin is a good model of secondary amyloidosis.

Light and electron microscopic studies of the spleen and liver from a patient with hereditary elliptocytosis have been reported. Characteristic findings are congestion of the cordal space, diminished variation of the erythrocyte shape in the cord, relatively empty sinuses and erythrophagocytosis by the cordal macrophages. The same basic defect of the red cell membrane as has been documented in hereditary sperocytosis might be a possible explanation on the pathogenesis of this rare hemolytic anemia.

Heinz body anemia was experimentally produced in mice by phenylhydrazine injection and the mechanism of hemolysis was investigated. Both in acute and chronic experiments, the "culling" function of the spleen was more important in removing the red cells containing Heinz bodies than the "pitting" function. In addition to extravascular hemolysis, intravascular hemolysis in the spleen, liver and in the peripheral circulation was evident as manifested by the presence of ghost cells and hemosiderin deposition in the kidney. In the absence of the spleen, the liver can replace the function of the spleen to a certain extent and selective removal of Heinz bodies by the Kupffer cell was occasionally demonstrated. Deposition of yellowish-brown pigments was noted in the cordal macrophages and the Kupffer cells, but the precise nature of these pigments is unknown.

The first case of Farber's disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle-shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle-shaped cells were positive for periodic acid-Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane-bound storage inclusions which consisted of so-called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed.

Morphological changes of the spleen in splenomegalic liver cirrhosis (SLC) were studied. Comparisons with the normal spleen and the spleen of idiopathic portal hypertension (IPH) were made by (1) light microscopy with histometry, (2) scanning electron microscopy (SEM) with histometry, and (3) SEM of the spleen vascular replica. Histometrical studies by light microscopy showed that in both SLC and IPH, the white pulp volume was decreased in random units of splenic tissue but increased in the whole spleen, whereas the red pulp volume was increased both in random units of splenic tissue and in the whole spleen. The increase in the total volume of the white pulp was less marked in SLC than in IPH. SEM histometry demonstrated in the red pulp an increase in small venous sinuses and narrowing of the Billroth cord in SLC and IPH. Narrowing of the Billroth cord was more marked in SLC than in IPH. SEM of the white pulp showed channels formed by reticulum cells around the central artery in SLC and IPH. The channels are thought to correspond to so-called "follikuläre Fibroadenie" or periarterial fibrosis. The spleen vascular replica demonstrated open arterial termination into the tissue spaces in the Billroth cord in SLC, IPH and the normal. Venous sinuses were arranged in bundles in SLC and IPH.

The first autopsy case of a patient treated with Perfluorochemicals (PFC, fluorocarbon) for hemolytic anemia, occurring after an operation for dissecting aneurysm, is reported. The results of preliminary experiments on the effects of histopathological manifestation of tissue with the administration of Perfluorochemicals in rabbit are also described. Both in human and experimental materials, the reticuloendothelial organs, blood monocytes and macrophages including histiocytes were markedly blocked in their phagocytic activities in every portion of the organs examined, and transformed themselves into ballooning foamy cells upon administration of PFC. Morphologically, the excretion of this chemical from either the lung or the urinary system can not be certified. The particles compatible to Perfluorochemicals are still found in the cytoplasm of cells in various organs, a full four months after the administration of Perfluorochemicals in the experiments. It is evident that further studies are necessary, regarding the use of Perfluorochemical in human beings.

A large number of foamy cells were noted in the spleens from fourteen ITP patients, and two patients who received a large amount of platelet rich plasma. Using the unlabelled immunoperoxidase method, these foamy cells were shown to contain platelet antigen. Platelets in varying stages of intracellular digestion, from intact-appearing forms to myelin-like materials, were disclosed in foamy cells. Foamy cells were experimentally induced in granulomas by subcutaneous injection of platelets with or without accompanied administration of steroid, the platelets reacted with anti-murine platelet antibody, commercialized phospholipids (PE, PC, SM, PS, and the mixture of them), and the red blood cell membrane. The foamy cells induced by the subcutaneous injection of platelets are similar to those in the spleens of ITP patients. The lipid in foamy cells is chiefly derived from the membrane phospholipid of injected platelets. Concentric myelin-like materials were also noted in the foamy cells after injection of erythrocyte membrane. The myelin-like materials in these foamy cells are similar to those appearing in macrophages following injection of PC and SM. This suggests that these phospholipids derived from cell membrane are more resistant to intracellular digestion by lysosomal enzymes. We conclude that the foamy appearance of the cordal macrophage in ITP spleens results from incomplete intracellular degradation of platelet membrane.

An autopsy case of a 10-year, 8-month-old boy with Hunter's syndrome is reported with emphasis on the ultrastructural findings of almost all the organs, except the brain. Intracytoplasmic inclusion bodies were observed in various organs as follows: nerve cells and glia in the spinal cord, hepatocytes and Kupffer cells in the liver, sinusoidal endothelium of the spleen, proximal tubules, podocytes and epithelium of Bowman's capsule of the kidney, interstitial fibroblast-like cells among cardiac muscle bundles, cardiac valves and aorta, exocrine and endocrine cells of the pancreas, adrenocortical cells, follicular epithelial cells of the thyroid. Leydig cells of the testis, chondrocytes, fibroblasts and endothelium of capillaries throughout the body. Three types of inclusion bodies were morphologically distinguishable. Type 1: clear vacuole, Type 2: zebra body, Type 3: clear vacuole with a lipid-like lamellar structure. The clear vacuole (Type 1) was thought to represent an accumulation of glycosaminoglycans, and the zebra body (Type 2), probably ganglioside. The type 3 inclusion body might be an intermediate and mixed form of the type 1 and type 2 inclusions. Histochemical study also suggested that the type 3 inclusion body contained glycosaminoglycan and a type of lipid.

Clinicopathologic findings of a case of familial hemophagocytic reticulosis (FHR), for which splenectomy, and biopsy of the liver and mesenteric lymph nodes were performed, is reported. Histologically, the proliferated cells consisted of not only histiocytes showing severe erythrophagocytosis, but also lymphoid cells of various sizes. The lymphoid cells had atypical features including mitotic figures and convoluted nuclei, and were suspected to be T cells as a result of immunohistochemical studies. We therefore consider that FHR is a special type of lymphoproliferative disease accompanied by severe proliferation of erythrophagocytic histiocytes rather than being a true histiocytic disease. Cytochemical and electron microscopic findings of the involved spleen are also presented.

Morphological changes in the spleens of patients with idiopathic portal hypertension (IPH) were studied and compared with the normal spleen. The study used (1) light microscopy with histometry, (2) scanning electron microscopy (SEM) of the splenic tissue with histometry and (3) SEM of the spleen vascular replica. Histometrical studies by light microscopy showed that the volume of red pulp of IPH was increased in a unit area and to a total of 12 times the normal in the whole spleen. The white pulp was scanty of lymphocytes and decreased in a unit area but it was increased in the whole spleen. SEM of the white pulp of IPH demonstrated many channels formed by reticulum cells and running parallel with each other along the central artery. This finding presumably corresponds to periarterial fibrosis in light microscopy. SEM histometry demonstrated that the venous sinuses of IPH were small but increased in number and occupied the same percentage area in a unit red pulp area as in the normal spleen. The Billroth cord of IPH was narrowed and occupied by thickened reticulum cells, which may cause increased pooling and destruction of blood cells in the enlarged spleen (hypersplenism). SEM of the tissue and vascular replica demonstrated open arterial termination in the Billroth cord in the spleen of IPH as well as in the normal spleen. Venous sinuses in the replica of IPH ran parallel with each other forming bundles with fewer intercommunications than normal.