Evidence for endothelial cell origin of vinyl chloride-induced hepatic angiosarcoma.

Previous reports of hepatic angiosarcoma have not clearly defined the cellular type from which this tumor arises, as evidenced by the terminology of endothelioma, Kupffer cell sarcoma, endothelial cell sarcoma, and hemangioendothelial sarcoma, etc., which have been used interchangeably. In addition, there has been no consensus on the separate entity of Kupffer and sinusoidal endothelial cells. In the work presented here, evidence for the endothelial cell origin of this tumor is provided by the demonstration of factor VIII, a known endothelial cell marker, in the tumor cells. Fluorescence due to the presence of factor VIII appeared intense in the tumor sinusoidal cells of all four vinyl chloride-associated angiosarcomas studied, whereas normal liver sinusoidal lining cells showed negligible fluorescence.

Occurrence of a thermostable antigen of ovarian carcinoma in normal tissues and secretions.

Thermostable antigen (TA) occurs in ovarian carcinoma and in certain specialized tissues. High titers of TA were found in nineteen of twenty endocervical extracts but not in myometrium, endometrium, or exocervix. TA was present in all of sixteen cervical mucus samples. Antibodies to perchloric acid extract of bronchus showed cross-reaticity with TA from ovarian carcinoma and cervix. Immunofluorescence with frozen sections revealed TA to be present in the columnar epithelium of ovarian neoplasms, and endocervical glands, in bronchial seromucous glands and in hepatic bile canaliculi. Immunofluorescence and immunodiffusion were used to test for cancer patient antibodies against TA. All sera tested negative. An immunofluorescence inhibition test for circulating TA also tested negative in sera of ovarian and cervical cancer patients.

Naturally occurring immune-complex glomerulonephritis in monkeys (Macaca irus). I. Light, immunofluorescence and electron microscopic studies.

Light, immunofluorescence and electron microscopic studies were carried out on renal biopsies from 32 randomly selected adult monkeys (Macaca irus). Histopathology was limited to glomeruli and consisted of mild to moderate segmental increases in mesangial cells, mesangial matrix, and/or glomerular basement membrane (GBM) thickness in 41% of the animals. Granular deposits of IgM were present in the mesangial region and along the GBM in 72% of the monkeys, whereas IgG, C1q, C4 and C3 were detected in approximately 30%. Electrondense deposits were seen predominantly in epithelial foot processes adjacent to the GBM and, to a lesser extent, in the mesangium. Those monkeys with the heaviest IgM deposition were found to have decreased serum levels of C3, IgM and IgA. Follow-up biopsies over a period of 3 to 11 months revealed that the disease process was persistent yet nonprogressive. No correlation with age or sex was noted. All animals examined were clinically healthy and had normal renal function. This is the first documented occurrence of spontaneous immune-complex glomerulonephritis in a large monkey population. It appears to be a persistent disease which does not progress to renal insufficiency and which may serve as an investigative model for mild nonprogressive forms of human glomerulonephritis.

A study of weak subgroups of blood group A with an antiglobulin-latex test.

The distribution of the blood group A antigen on subgroups A1, A2, A3, Ax, and Ae1 was studied by means of a highly sensitive and specific antiglobulin-latex test. Marked variability in the cell to cell expression of A antigen was observed in A1 and A2 cells. The weaker subgroups (A3, Ax, and Ae1) were characterized by a minor population of cells containing A antigen and a major population with no detectable A sites. Comparison of the antiglobulin-latex test with the fluorescent antibody technique indicates that the former is approximately 10,000 times more sensitive in detecting cell bound antibody, and thereby membrane antigens. The results of this study demonstrate that within each of the A subgroups (with the possible exception of A1) there exist erythrocytes that apparently lack recognizable A antigen sites. The number of such cells is greatest in the weakest subgroups (Ax and Ae1).

Activation of the alternate complement pathway by autologous red cell stroma.

The present study demonstrates the ability of human autologous RBC stroma to activate the alternate complement pathway (C3-Activator system, properdin system), as evidenced by the generation of C3-Activator (C3A) from C3-Proactivator (C3PA) when RBC ghosts and sonicated ghosts are incubated with autologous serum. Intact RBC's, hemoglobin, and concentrated platelet stroma, on the other hand, are inactive in this regard. We postulate that this in vitro activity of RBC stroma may occur intravascularly when erythrocytes are damaged by immune or nonimmune mechanisms. The ensuing interaction of activated complement components with platelets leading to release of platelet factor three (PF-3) may constitute a mechanism for activation of the coagulation system during acute hemolytic episodes.