Phase I-II study of the addition of alpha-2a interferon to 5-fluorouracil/leucovorin. Pharmacokinetic interaction of alpha-2a interferon and leucovorin.

5-Fluorouracil (5-FU) activity has been improved by the use of leucovorin (LV) or alpha-2a interferon (alpha-IF). We investigated the feasibility and activity of addition of alpha-IF to a 5-FU/LV regimen. A phase I study with 26 patients (14 previously untreated, 12 previously treated) with disseminated cancer was conducted.

The cellular immune response to cell-associated and cell-free cytomegalovirus (CMV) antigens after primary CMV-infection in non-immunocompromised hosts: development and maintenance of CMV-latency and its influence on immunocompetence.

Development and maintenance of cellular immunity to cell-associated CMV-antigens (CMVFF) was investigated in non-immunocompromised hosts during the first year (group I, n = 11) and 1 to 5 years (group II, n = 9) after a symptomatic primary CMV infection, as well as in healthy CMV-seropositive controls without a history of CMV disease (group III, n = 28). During the acute phase (0-2 months) of a primary CMV-infection CMVFF-induced lymphocyte proliferation was severely decreased compared to that in the post-illness phase (5-12 months), and to that in groups II and III. After the reconvalescent period (3-4 months) it gradually increased to levels seen in group III.

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation.

To study genetically determined susceptibility to cytomegalovirus and herpes simplex virus infections in patients given renal transplants a prospective study was performed of 68 consecutive patients receiving their first cadaveric kidney allograft. The recipients positive for HLA-DRw6 showed a significantly increased incidence of active cytomegalovirus infection as early as the 10th week after transplantation (p less than 0.05).

Maintenance of cytomegalovirus (CMV) latency and host immune responses of long term renal allograft survivors. II. Secondary CMV infections associated with impaired in vitro proliferative responses to mitogens, allogeneic lymphocytes and CMV infected cells.

The relationship between secondary cytomegalovirus (CMV) infections and host general cellular immunocompetence was investigated in 16 renal allograft recipients with minimal immunosuppressive treatment and excellent renal function. Results were compared with 19 CMV seropositive healthy controls. Significantly impaired immune responses were detected in the subgroup of nine recipients who experience at least 2 years before a secondary CMV infection.

Maintenance of cytomegalovirus (CMV) latency and host immune responses of long term renal allograft survivors. I. Prolonged suppression of in vitro lymphocyte responses against CMV infected fibroblasts related to previous secondary CMV infection.

Cytomegalovirus (CMV) specific humoral and cellular immunity was investigated in 16 renal allograft recipients with long term graft survival (26-122 months) who were shown to be CMV seropositive before transplantation. Results were compared with healthy individuals with latent CMV infections. Recipients (n = 9) who experienced a symptomatic secondary CMV infection shortly after transplantation (less than 6 months), showed a prolonged but finally temporary suppression of their in vitro lymphocyte memory responses against CMV infected fibroblasts (CMV-FF; median SI: 1.

A stimulatory role for cytomegalovirus (CMV) antibodies in CMV-specific lymphocyte proliferation in vitro.

Cytomegalovirus(CMV)-specific lymphocyte proliferation in vitro was tested in the presence or absence of CMV-specific antibodies. CMV antibodies clearly enhanced CMV-specific lymphocyte proliferation but not lymphocyte proliferation induced by other antigens. Enhancement was most consistently found with cell-bound CMV antigens and often with cell-free CMV as stimulating antigen.

Comparison of in vitro lymphocyte proliferations induced by cytomegalovirus-infected human fibroblasts and cell-free cytomegalovirus.

In vitro lymphocyte reactivity (LR) to cytomegalovirus (CMV)-infected human fetal fibroblasts (CMVFF) and cell-free CMV were measured by using lymphocytes from healthy donors. Lymphocytes from all seropositive donors were stimulated by CMVFF, whereas lymphocytes from negative donors were not. The optimal stimulator cell-to-lymphocyte ratio was in the range of 1:5 to 1:50, dependent on the virus dose used.