Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease.

Infections occurring 6 mo or later after bone marrow transplantation for severe aplastic anemia or hematologic malignancy were analyzed in 98 long-term survivors. Varicella-zoster (VZ) infections were analyzed separately from all other infections. The factor predisposing most strongly to late VZ infection was genotypic nonidentity for HLA between marrow donor and recipient.

Cyclosporin-A abrogates transfusion-induced sensitization and prevents marrow graft rejection in DLA-identical canine littermates.

Previous studies had shown that marrow graft rejection generally did not occur in untransfused dogs given 900-rad total body irradiation and hemopoietic grafts from DLA identical littermates (only 1 of 59 rejected), but was seen in all instances after three preceding transfusions of whole blood from the marrow donor on days -24, -17, and -10 before transplantation (19 of 19 rejected). The present study was undertaken to investigate whether immunization by 3 preceding transfusions of whole blood from the DLA-identical littermate marrow donor could be abrogated by administration of the immunosuppressive agent cyclo-sporin-A, 20 mg/kg/day intramuscularly on days -5 to 0. Seven of 10 dogs showed sustained marrow engraftment.

Acute and chronic graft-versus-host disease in dogs given hemopoietic grafts from DLA-nonidentical littermates. Two distinct syndromes.

We recognized two distinct clinical and histologic syndromes of acute and chronic graft-versus-host disease (GVHD) in irradiation chimeric dogs given hemopoietic grafts from DLA-nonidentical littermate donors. Clinically acute GVHD developed, with a median onset of 13 days after the transplant, and was characterized by skin erythema, jaundice, diarrhea, and gram-negative infections; the median survival of these dogs was 29.5 days.

Properties of particulate and solubilized phosphatidylserine synthase activity from Saccharomyces cerevisiae. Inhibitory effect of choline in the growth medium.

When radiolabeled serine is incubated with a particulate fraction from Saccharomyces cerevisiae, radioactivity is incorporated initially into phosphatidylserine and gradually appears in phosphatidylethanolamine. Because decarboxylation of phosphatidylserine is blocked by hydroxylamine, phosphatidylserine synthase can be assayed separately. The yeast phosphatidylserine synthase activity 1) exhibits a divalent cation requirement; 2) is stimulated by exogenous CDP-diolein (apparent Km = 0.

Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of intolerance.

We examined the effect of methotrexate (MTX) and cyclosporin A (Cy A) on engraftment, graft-versus-host disease (GVHD), and the induction of tolerance in dogs prepared for marrow transplantation by 9 Gy of total body irradiation and grafted with bone marrow and buffy coat cells. Nineteen dogs were given grafts from DLA-identical littermates followed by immunosuppression with Cy A for 25 or 100 days. All had sustained engraftment, and 12 became healthy long-term chimeras.

Molecular cloning and amplification of the gene for thymidylate synthetase of E. coli.

The thyA gene of Escherichia coli, which directs the synthesis of the enzyme thymidylate synthetase, has been subcloned from a recombinant lambda phage (Hickson et al., 1982) into the multicopy plasmid pBR325 to give the plasmid pPE245. To identify the thyA gene product, the transposon Tn1000 was inserted into pPE245 and derivative plasmids isolated that were no longer able to complement thyA mutations.

T-cell subpopulations identified by monoclonal antibodies after human marrow transplantation. I. Helper-inducer and cytotoxic-suppressor subsets.

Peripheral blood helper-inducer and cytotoxic-suppressor T-cell subpopulations in patients receiving marrow transplants for the treatment of acute leukemia or severe aplastic anemia were quantitated on the fluorescence-activated cell sorter (FACS) using the monoclonal antibodies OKT4 and OKT8, respectively. The relative (percent) and absolute number of OKT4+ cells were severely and persistently depleted for up to 2.7 yr posttransplant.

Low serum thymic hormone levels in patients with chronic graft-versus-host disease.

We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis.

Construction of recombinant lambda phages that carry the E. coli recB and recC genes.

A fragment of the E. coli chromosome including the recC gene has been cloned by in vitro recombinant DNA techniques into a phage lambda vector to give the recombinant phage lambda drecC. This was used to derive the phage lambda drecBC by in vivo recombination.

Protein synthesis in vivo by Schistosoma mansoni cercariae.

Cercariae of Schistosoma mansoni were labeled with [14C]leucine in vivo and their protein studied by one- and two-dimensional electrophoretic fluorography. With molecular weight (Mr) and isoelectric point (pI) as parameters, polypeptides from different stages of cercarial embryogenesis were compared with each other and with those of adult worms. Up to six polypeptides with different isoelectric points were found in a single electrophoretic band of the same Mr.

Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment.

One-hundred fifty-three recipients of HLA-identical sibling marrow transplants for aplastic anemia or hematologic malignancy were injected with bacteriophage phi X174 (phage), pneumococcal polysaccharide antigen (PPA), or keyhole limpet hemocyanin (KLH). Antibody levels were determined several times in the 6 wk after injection. Multiple regression techniques were used to determine what factors played significant roles in the antibody response.

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression.

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases.

Colorectal anastomosis by transanal end-to-end stapling.

In 26 patients end-to-end colorectal anastomosis was attempted using a transanal stapling instrument. The anastomosis was successful in 19 patients. Permanent colostomy would have been the only alternative treatment in 12 patients.

Canine lymphocyte subpopulations.

Ten to 23% of cells in blood, lymph node and bone marrow from normal dogs formed rosettes with human erythrocytes, and 12-27% formed rosettes with erythrocyte-antibody-complement (EAC) complexes. In contrast, only 3% of thymocytes, and 1% of thoracic duct cells formed rosettes with human erythroyctes, and 0 and 15% respectively formed EAC rosettes. When peripheral blood mononuclear cells were separated by rosette sedimentation into populations depleted of, or enriched for, cells forming rosettes with human erythrocytes (H-RFC), the population depleted of H-RFC responded more vigorously to alloantigens in mixed leukocyte culture (MLC) (P < 0.

Yeast mutant defective in phosphatidylserine synthesis.

Phospholipid biosynthesis in a mutant of Saccharomyces cerevisiae (cho1) which lacks phosphatidylserine (Atkinson, K. D., Jensen, B.

Recurrent reproductive failure due to severe placental villitis of unknown etiology.

A case is reported of recurrent reproductive failure due to a severe placental villitis of unknow etiology. Five successive pregnancies ended in four unexpected third-trimester deaths in utero and one live birth at 37 weeks' gestation. This infant of the fourth pregnancy showed severe intrauterine growth retardation but no other stigmata of chronic infection.

Yeast mutants auxotrophic for choline or ethanolamine.

Three mutants of the yeast Saccharomyces cerevisiae which require exogenous ethanolamine or choline were isolated. The mutants map to a single locus (cho1) on chromosome V. The lipid composition suggests that cho1 mutants do not synthesize phosphatidylserine under any growth conditions.