ABSTRACT
The surface-associated molecules of the invasive stages of apicomplexan parasites such as Neospora caninum and Toxoplasma gondii are most likely crucially involved in mediating the interaction between the parasite and its host cell. In N. caninum, several antigens have recently been identified which could participate in host cell adhesion and/or invasion. These are antigens which are either constitutively expressed on the outer plasma membrane, or antigens which are only transiently localised on the surface as they are expulsed from the secretory vesicles either prior, or after host cell invasion. Some of these proteins have been characterised at the molecular level, and it has been shown that they are, with respect to protein sequences, closely related to homologous counterparts in T. gondii. Nevertheless, there is only a low degree of cross-antigenicity between the two species. In microbial interactions it has been shown that carbohydrates could also play a crucial role in host cell recognition and immunological host parasite interactions. In this study we present data which strongly suggest that the surface of N. caninum tachyzoites is glycosylated. In SDS-PAGE, glycoproteins comigrated largely with glycosylphosphatidylinositol-anchored proteins which were identified using in vivo [3H]ethanolamine labelling followed by autoradiography. The lectin Con A reacted strongly with the surface of these parasites, binding of which is indicative for the presence of N-glycans. Additional surface binding was observed, although only in a subpopulation of all tachyzoites, for wheat germ agglutinin and Jacalin. Intracellular binding sites for Con A were mainly associated with the parasite dense granules. By lectin labelling of Western blots of N. caninum protein extracts, glycoproteins were identified which reacted specifically with the lectins Con A, wheat germ agglutinin, Jacalin and soy bean agglutinin.
Subject(s)
Antigens, Protozoan/analysis , Glycoconjugates/analysis , Glycoproteins/analysis , Neospora/chemistry , Neospora/growth & development , Animals , Antigens, Protozoan/chemistry , Antigens, Surface/analysis , Antigens, Surface/chemistry , Binding Sites , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Glycoconjugates/chemistry , Glycoproteins/chemistry , Gold , Lectins/metabolism , Microscopy, Electron , Neospora/immunologySubject(s)
ABO Blood-Group System , Blood Group Incompatibility , Graft Rejection/immunology , Graft Survival , Kidney Transplantation/immunology , Adult , Antibody Formation , Drug Therapy, Combination , Female , Graft Rejection/pathology , Graft Rejection/therapy , Histocompatibility Testing , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/mortality , Kidney Transplantation/pathology , Living Donors , Male , Plasmapheresis , Survival AnalysisSubject(s)
ABO Blood-Group System , Blood Group Incompatibility , Graft Survival/drug effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Adult , Antilymphocyte Serum/therapeutic use , Azathioprine/therapeutic use , Drug Therapy, Combination , Graft Rejection/drug therapy , Graft Rejection/epidemiology , Graft Rejection/immunology , Guanidines/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/mortality , Kidney Transplantation/physiology , Male , Methylprednisolone/therapeutic use , Middle Aged , Survival Rate , Tacrolimus/adverse effectsABSTRACT
BACKGROUND: Despite great efforts to promote the donation of cadaveric organs, the number of organ transplantations in Japan is not increasing and a serious shortage of cadaveric organs exists. These circumstances have forced a widening of indications for kidney transplantation. For this purpose, ABO-incompatible living kidney transplantations (LKTs) have been performed. Although we have already reported the short-term results of ABO-incompatible LKT, there is no report of long-term results in such cases; anti-A and anti-B antibodies could cause antibody-induced chronic rejection and result in poor long-term graft survival. In this study, we have reviewed the long-term results of ABO-incompatible LKT and tried to identify the most important factors for long-term renal function in ABO-incompatible LKT. METHODS: Sixty-seven patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January, 1989, and December, 1995. The mean age was 34.9 years (range, 8-58 years), with 38 males and 29 females. Incompatibility in ABO blood group antigens was as follows: A1-->O, 23 patients; B-->O, 19 patients; A1B-->A1, 7 patients; B-->A1, 8 patients; A1-->B; 4 patients; A1B-->B, 4 patients; A1B-->O, 2 patients. The number of HLA-AB, and -DR mismatches were 1.6+/-1.1 and 0.76+/-0.6, respectively. Plasmapheresis and immunoadsorption were carried out to remove the anti-AB antibodies before the kidney transplantation. In the induction phase, methylprednisolone, cyclosporine, azathioprine, antilymphocyte globulin, and deoxyspergualin were used for immunosuppression. Local irradiation of the graft was performed at a dose of 150 rad, on the first, third, and fifth days after transplantation. Splenectomy was done at the time of kidney transplantation in all cases. RESULTS: Patient survival was 93% at 1 year and 91% at 8 years. Graft survival was 79% at 1, 2, 3, and 4 years, 75% at 5 and 6 years, and 73% at 7 and 8 years. Patient survival was not significantly different from that of ABO-compatible patients. However, graft survival was significantly different between ABO-incompatible grafts and ABO-compatible grafts. Specifically, ABO-incompatible transplant recipients experienced a significantly higher rate of early graft loss up to 3 years but showed an equivalent graft loss by year 4. Among 67 patients, 16 grafts were lost during the observation period. Loss was due to acute rejection in 5 patients, followed by chronic rejection in 5 patients and death with function in 3 patients, whereas immunosuppression was withdrawn in 3 patients due to nonimmunological reasons. Of 16 grafts lost, 15 were lost within 1 year after transplantation. Of the 67 patients, 5 died during observation. Three patients with functioning grafts died of uncontrolled bleeding due to duodenal ulcer, malignant lymphoma, and cerebral hemorrhage (one patient each). One patient died of ischemic colitis due to secondary amyloidosis and one patient of cerebral hemorrhage after graft loss due to humoral rejection. There was no fatal infectious complication, whereas 10 patients had non-tissue-invasive cytomegalovirus infection. The stepwise logistic regression model was employed to identify the most important factors for long-term renal function. Patients were subdivided into those with serum creatinine of less than 2.0 mg/dl (group 1, n=39) versus those with serum creatinine of more than 2.0 mg/dl (group 2, n=22) at one year after renal transplantation. Six patients were excluded because of death with functioning graft (three patients) and withdrawal of immunosuppression (three patients). Rejection episodes within 6 months were significantly frequent in group 2 compared with group 1 (P=0.0008). Odds ratio was 112-fold in the rejection episodes. Obviously, the high incidence of early humoral rejection is caused by ABO incompatibility, because ABO-incompatible grafts experience a higher rate of early rejection and graft loss compa
Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Kidney Transplantation/immunology , Tissue and Organ Procurement , Transplantation Immunology , Adolescent , Adult , Child , Female , Histocompatibility , Humans , Immunosorbents , Immunosuppression Therapy , Japan , Kidney Failure, Chronic/surgery , Likelihood Functions , Logistic Models , Male , Middle Aged , Plasmapheresis , Transplants/supply & distributionSubject(s)
Kidney Transplantation/physiology , Pregnancy Complications/epidemiology , Pregnancy , Adolescent , Adult , Creatinine/blood , Female , Follow-Up Studies , Graft Rejection/epidemiology , Graft Survival , Humans , Immunosuppression Therapy/methods , Puerperal Disorders/epidemiology , Retrospective Studies , Time FactorsSubject(s)
Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation/immunology , Ribonucleosides/pharmacokinetics , Adult , Creatinine/metabolism , Half-Life , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Lymphocyte Culture Test, Mixed , Lymphocytes/drug effects , Lymphocytes/immunology , Metabolic Clearance Rate , Regression Analysis , Ribonucleosides/adverse effects , Ribonucleosides/therapeutic useSubject(s)
Angioplasty, Balloon , Hypertension, Renovascular/therapy , Kidney Transplantation , Blood Pressure , Creatinine/blood , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Hypertension, Renovascular/etiology , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Middle Aged , Postoperative ComplicationsSubject(s)
Diabetes Mellitus/epidemiology , Immunosuppressive Agents/adverse effects , Kidney Transplantation/immunology , Tacrolimus/adverse effects , Adolescent , Adult , Diabetes Mellitus/chemically induced , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/epidemiology , Female , Follow-Up Studies , Glucose Tolerance Test , Histocompatibility Testing , Humans , Male , Methylprednisolone/therapeutic use , Postoperative Complications , Risk Factors , Time FactorsSubject(s)
Graft Survival , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Muromonab-CD3/therapeutic use , Adult , Creatinine/blood , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Kidney Transplantation/mortality , Kidney Transplantation/physiology , Male , Retrospective Studies , Survival Rate , Time FactorsSubject(s)
ABO Blood-Group System , Blood Group Incompatibility , Graft Rejection/pathology , Kidney Transplantation/immunology , Antibody Formation , Biopsy, Needle , Graft Rejection/immunology , Humans , Immunity, Cellular , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/pathology , SplenectomySubject(s)
Graft Survival , Hepatitis C/prevention & control , Hepatitis C/transmission , Interferon-alpha/therapeutic use , Kidney Transplantation , Tissue Donors , Adolescent , Adult , Female , Follow-Up Studies , Histocompatibility Testing , Humans , Kidney Transplantation/immunology , Kidney Transplantation/physiology , Male , Middle Aged , Polymerase Chain Reaction/methods , RNA, Viral/analysisSubject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , Cytomegalovirus Infections/diagnosis , Kidney Transplantation , Polymerase Chain Reaction/methods , Postoperative Complications , Adolescent , Adult , Base Sequence , Child , Child, Preschool , DNA Primers , DNA, Viral , Enzyme-Linked Immunosorbent Assay/methods , Female , Histocompatibility Testing , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Kidney Transplantation/immunology , Leukocytes/virology , Male , Middle Aged , Molecular Sequence DataSubject(s)
Glomerulonephritis, IGA/physiopathology , Graft Rejection/epidemiology , Kidney Transplantation/physiology , Postoperative Complications , Proteinuria , Adult , Female , Glomerulonephritis, IGA/pathology , Graft Rejection/pathology , Humans , Hypertension/physiopathology , Kidney Function Tests , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Male , Prognosis , Retrospective Studies , Risk FactorsSubject(s)
ABO Blood-Group System , Blood Group Incompatibility , Graft Survival/immunology , Kidney Transplantation/immunology , Acute Disease , Adolescent , Adult , Cause of Death , Child , Chronic Disease , Female , Graft Rejection/epidemiology , Histocompatibility Testing , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Survival Rate , Time FactorsABSTRACT
The effects of the addition of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, to the medium on sterol synthesis and phosphatidylcholine (PC) synthesis were studied in HepG2 cells. The cells were cultured with simvastatin at concentrations of 10(-7) and 10(-6) mol/L for 6 hours, and radioactive lipid precursors were added 1 hour before harvesting. Simvastatin inhibited cholesterol synthesis from [14C]acetate in a dose-dependent manner. It also decreased the incorporation of [14C]choline into PC by 30%; this decrease was accompanied by a decrease in phosphocholine cytidylyltransferase activity in cell homogenates. Simvastatin had no significant effects on the incorporation of [3H]glycerol into phospholipids. These data indicate that simvastatin has two different functions: inhibition of HMG-CoA reductase and depression of de novo synthesis of PC via the cytidine diphosphate-choline pathway, which, in turn, may result in a decrease in plasma lipid levels.
Subject(s)
Anticholesteremic Agents/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Lovastatin/analogs & derivatives , Phosphatidylcholines/biosynthesis , Cholesterol/biosynthesis , Choline/metabolism , Choline Kinase/metabolism , Dose-Response Relationship, Drug , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/metabolism , Lovastatin/pharmacology , Simvastatin , Tumor Cells, CulturedSubject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Cesarean Section , Kidney Transplantation , Adult , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Pregnancy , Pregnancy Complications/surgery , Time FactorsSubject(s)
ABO Blood-Group System , Kidney Transplantation , Kidney Transplantation/physiology , Adult , Antilymphocyte Serum/therapeutic use , Azathioprine/therapeutic use , Creatinine/blood , Cyclosporine/therapeutic use , Female , Graft Survival , Guanidines/therapeutic use , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Survival Analysis , Time FactorsABSTRACT
We performed in total 528 kidney transplantations from Feb. 1983 to Dec. 1988 in Kidney Center of Tokyo Women's Medical College. Of the 528 kidney transplantations, 450 were living related kidney transplantations. The living related renal transplant recipients treated with CYA were divided into 3 groups: high dose CYA double drug therapy group (group 1), high dose CYA triple drug therapy group (group 2) and low dose CYA triple drug therapy group (group 3). Group 1 (n = 263) was treated with CYA (initial dose 12 mg/kg) and methylprednisolone (MP). Group 2 (n = 106) was treated with CYA (initial dose 10 mg/kg), MP and azathioprine (AZ) (1 mg/kg). Immunosuppression of group 3 (n = 81) consisted of CYA (initial dose 6 mg/kg), MP and AZ (2 mg/kg) (or mizoribine (MZ) (3-5 mg/kg). CYA serum trough level (polyclonal) was lowered according to the initial dose of CYA, and in particular trough level in group 3 was controlled at a low level (50-150 ng/ml in induction phase) to reduce CYA nephrotoxicity. However, even if strict control of serum trough level was accomplished, we could not get improvement of renal function in Group 3. Group 3 had more frequent and severe accelerated acute rejections (AAR) than the other groups. These data showed that inadequate immunosuppression in group 3 caused more frequent and severe rejection episodes. Also, renal biopsy revealed CYA nephrotoxicity even in group 3 and this nephrotoxicity may have been caused by ischemic damage by severe rejections.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Cyclosporins/administration & dosage , Kidney Transplantation , Tissue Donors , Adult , Aged , Female , Graft Rejection/drug effects , Humans , Immunosuppression Therapy , Male , Middle AgedABSTRACT
A modified hemoglobin solution (