Serum total bile acids monitoring after experimental orthotopic liver transplantation

The aim of this study was to evaluate the usefulness of serum total bile acids estimation in monitoring liver allograft recipients. To this end frequent blood samples and simultaneous needle biopsies of the liver were taken after orthotopic liver transplantation in unimmunosuppressed pigs. Serum bile acids were found to rapidly increase during the anhepatic phase of the transplantation procedure and to decrease after implantation of the liver graft. A normal serum bile acids level in the early postoperative phase was indicative of a technically successful transplantation procedure. A total of 28 successful transplantations was performed. Six recipients accepted the allograft without any histological sign of rejection. In 18 pigs the liver was rejected, the survival time of these animals ranged from 6 to 80 days. Four animals showed a transient rejection episode during the first months after transplantation. In nonrejecting animals serum bile acids remained undisturbed during the entire 4-month study period. In all cases of rejection serum bile acids promptly increased to very high levels of 100 to 700 mumol/liter (reference range 1 to 14 mumol/liter). Serum bile acids were found to be superior to standard liver function tests in detecting the process of liver rejection at an earlier stage. These results indicate that serum total bile acid estimation is a simple and useful test to monitor liver allograft recipients.     

Direct and immune-cell-mediated effects of Bacteroides gingivalis on bone metabolism in vitro

We investigated direct and immune-cell-mediated effects of Bacteroides gingivalis on bone metabolism in vitro. Fetal mouse long-bone rudiments were cultured under aerobic conditions in the presence of (a) intact bacteria, (b) low molecular weight (MW less than 1000) metabolic products of the bacteria, or (c) conditioned media of mouse spleen cells activated by whole bacteria. A suspension of intact bacteria, added directly to the bone culture, had no effect on bone resorption or bone formation. Low molecular weight (MW less than 1000) excretion products of the bacteria inhibited bone resorption and transiently reduced mineralization of the diaphysis, while the growth in length of the bones was not affected. However, conditioned media of bacteria-activated spleen cells strongly enhanced bone resorption and increased osteoclast numbers in the bone culture, while inhibiting mineral formation in the diaphysis. This led to a strongly negative mineral balance. These data do not support a direct effect of either bacteria or bacterial products on bone tissue as a likely explanation for bone loss in periodontal disease. Rather, they favour the concept that the loss of bone in this disease is an indirect effect of the host response, resulting from the contact of immune cells with the bacteria. This implies that bacterial invasion of the connective tissue of the gingiva may not be a prerequisite for alveolar bone loss.     

Surface markers and functional properties of non-Hodgkin's lymphoma cells in relation to histology.

Cells from 32 adult patients with non-Hodgkin's lymphoma were studied with respect to surface markers and functional properties in short-term culture. Twenty-six lymphomas were of B-cell origin, including all nodular and diffuse lymphocytic lymphomas. Three tumors were of T-cell origin (one histiocytic lymphoma and two undifferentiated lymphomas). In the remaining three cases (histiocytic lymphomas) the immunological nature of the tumor cells could not be determined. All reactivity to mitogenic stimuli of cells from B-cell lymphomas was due to residual normal T cells. In follicular lymphocytic lymphomas more reactive T cells prevailed among the malignant B cells than in diffuse lymphocytic lymphomas. Heterogeneity among B-cell lymphomas was indicated by differences in intensity of fluorescence with anti-Ig reagents and in stimulatory capacity in mixed lymphocyte culture. T-cell lymphomas were characterized by high percentages of T cells together with impaired responses to stimuli. The results of immunological studies correlated well with the histological classifications of Rappaport, Lukes and Lennert.     

CLL and diffuse histiocytic lymphoma in one patient: clonal proliferation of two different B cells.

A case report is presented of a 77-year-old woman suffering from a composite lymphoma, known as Richter's Syndrome, consisting of chronic lymphocytic leukaemia (CLL) and diffuse histiocytic lymphoma. Light-microscopic investigation revealed the presence of CLL cells in the blood and bone marrow and a combination of CLL cells and large immunoblastic cells in the lymph node. Immunological investigation showed that both malignant cell types were B cells. The CLL cells carried a monoclonal surface immunoglobulin (S-Ig) micron lambda, and the immunoblastic cells had a monoclonal S-Ig micron K. These findings indicated that both clonal lymphoproliferative diseases were probably derived from different tumour stem cells.     

CLL and Diffuse Histiocytic Lymphoma in One Patient: Clonal Proliferation of Two Different B Cells

A case report is presented of a 77-year-old woman suffering from a composite lymphoma, known as Richter's Syndrome, consisting of chronic lymphocytic leukaemia (CLL) and diffuse histiocytic lymphoma. Light-microscopic investigation revealed the presence of CLL cells in the blood and bone marrow and a combination of CLL cells and large immunoblastic cells in the lymph node. Immunological investigation showed that both malignant cell types were B cells. The CLL cells carried a monoclonal surface immunoglobulin (S-Ig) μΛ, and the immunoblastic cells had a monoclonal S-Ig μk. These findings indicated that both clonal lymphoproliferative diseases were probably derived from different tumour stem cells.     

Phytohemagglutinin skin test for the immunological assessment of the surgical patient

The use of phytohemagglutinin (PHA) as skin test agent was investigated. The test was performed in 42 healthy individuals and in 32 patients with malignant disease undergoing surgery. To establish immunosuppression in the direct postoperative period 15 patients undergoing cholecystectomy were tested sequentially. All healthy adults had a positive delayed response. No systemic or permanent local reactions were encountered. In healthy adults the PHA skin test had no influence on the in vitro PHA blastogenesis, the number of leukocytes, lymphocytes and E-rosette-forming cells. A reversion of the immunosuppressed state to normal in some cancer patients upon surgery was substantiated as well. The PHA skin test is an easy and a reliable method to give an impression of the immune response of surgical patients. It has many advantages above the commonly employed primary and secondary antigens.     

Bacteroides gingivalis stimulates bone resorption via interleukin-1 production by mononuclear cells The relative role for B. gingivalis endotoxin

Abstract. Supernatants of human peripheral blood mononuclear cells cultured in the presence of B. gingivalis , showed a strong osteoclast stimulating activity as measured by ⁴⁵Ca release from fetal mouse long bones in vitro. These supernatants also contained a high concentration of bioactive and immunoreactive interleukin-l (IL-1), but tumor necrosis factor (TNF a ), another osteoclast-activating cytokine, was not detected. Osteoclast activation by the supernatants was inhibited by an antibody against IL-1. whereas ultrapure human IL-1 mimicked the effect of the supernatant. The ability of B. gingivalis to induce IL-1 and OAF production was heat sensitive, as 20 min heating of the bacteria at 120°C caused a 50% loss of activity. In addition, purified B. gingivalis lipopolysaccharide (LPS) had little IL-1 inducing capacity, compared with LPS of Escherichia coli. These data suggest that human peripheral blood cells confronted with B. gingivalis produce large amounts of IL-1 which has strong osteoclast stimulating activity. However, in contrast with E. coli LPS, B. gingivalis LPS does not seem to be the major inducing agent. Thus other bacterial components must be responsible for the observed IL-1 and OAF induction.     

Proliferation of T gamma cells with killer-cell activity in two patients with neutropenia and recurrent infections

Two patients with severe granulocytopenia and recurrent infections of the skin and oropharynx had excess T lymphocytes with receptors for the Fc portion of IgG (T gamma cells) in blood and bone marrow. The abnormal T gamma cells killed antibody-sensitized target cells in vitro (killer-cell activity) but did not suppress immunoglobulin production by B lymphocytes (suppressor-cell activity). T gamma lymphocytes from normal persons showed both killer-cell activity and suppressor-cell activity. In the serum of one patient, granulocyte antibodies, possibly of an autoimmune nature, were detected. The clinical picture in conjunction with the hematologic and immunologic findings characterized the disease of both patients as a distinct entity among the chronic lymphoproliferative diseases of T-cell origin.     

Liver allograft rejection in pigs: Histology of the graft and role of swine leukocyte antigen-D

The porcine liver is often considered an immunologically privileged organ as liver allografts in unrelated pigs can survive without any form of immunosuppression. When donor and receptor animals were mismatched for swine leukocyte antigen-D (SLA-D) antigens as tested in mixedlymphocyte culture (MLC), liver allografts were rejected in all but one of the 14 cases studied. In contrast, from the 10 animals receiving a liver from an MLC-matched donor 8 survived without any significant sign of rejection. The diagnosis of rejection was made by histologic examination of serial needle biopsies of the liver. Based on survival time and histological type of cellular infiltrate an early and a late form of rejection could be distinguished. The early form, with a survival time from 6 to 10 days, was characterized by lymphocytic infiltration of the portal tracts and the liver parenchyma. The late form, with a survival time ranging from 15 to 80 days, showed a lymphocytic and plasma cellular infiltration of the portal tracts. These results show that the outcome of liver allotransplantation in pigs is strongly dependent on SLA-D histocompatibility. It is concluded that porcine liver allografts are under immunological control.