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I Doxiadis

Publications and source records attributed to I Doxiadis.

At least 19 recordsLinked to original sources
PubMed2003

The superior results of living-donor renal transplantation are not completely caused by selection or short cold ischemia time: a single-center, multivariate analysis.

BACKGROUND: The results of living-donor (LD) renal transplantations are better than those of postmortem-donor (PMD) transplantations. To investigate whether this can be explained by a more favorable patient selection procedure in the LD population, we performed a Cox proportional hazards analysis including variables with a known influence on graft survival. METHODS: All patients who underwent transplantations between January 1981 and July 2000 were included in the analysis (n=1,124, 2.6% missing values). There were 243 LD transplantations (including 30 unrelated) and 881 PMD transplantations. The other variables included were the following: donor and recipient age and gender, recipient original disease, race, current smoking habit, cardiovascular disease, body weight, peak and current panel reactive antibody, number of preceding transplants and type and duration of renal replacement therapy, and time since failure of native kidneys. In addition, the number of human leukocyte antigen identical combinations, first and second warm and cold ischemia periods, left or right kidney and fossa, donor kidney anatomy, donor serum creatinine and proteinuria, and transplantation year were included. RESULTS: In a multivariate model, donor origin (PMD vs. LD) significantly influenced the graft failure risk censored for death independently of any of the other risk factors (P=0.0303, relative risk=1.75). There was no time interaction. When the variable cold ischemia time was excluded in the same model, the significance of the influence of donor origin on the graft failure risk increased considerably, whereas the magnitude of the influence was comparable (P=0.0004, relative risk=1.92). The influence of all other variables on the graft failure risk was unaffected when the cold ischemia period was excluded. The exclusion of none of the other variables resulted in a comparable effect. Donor origin did not influence the death risk. CONCLUSION: The superior results of LD versus PMD transplantations can be partly explained by the dichotomy in the cold ischemia period in these populations (selection). However, after adjustment for cold ischemia periods, the influence of donor origin still remained significant, independent of any of the variables introduced. This superiority is possibly caused by factors inherent to the transplanted organ itself, for example, the absence of brain death and cardiovascular instability of the donor before nephrectomy.

Adult↗
PubMed1999

Genotyping for human platelet-specific antigens HPA-1, -2, -3, -4 and -5 in the Slovenian population reveals a slightly increased frequency of HPA-1b and HPA-2b as compared to other European populations.

Typing of human platelet alloantigens (HPA) is necessary in various clinical situations. The purpose of this study was to type a random sample of the Slovenian population for HPA alleles, in order to obtain genetic population data. A total of 152 unrelated Slovenian blood donors were genotyped for HPA-1, -2, -3, -4 and -5 alleles using a simple method that enables simultaneous and complete determination of HPA genotypes. Ten different polymerase chain reactions employing sequence-specific priming (PCR-SSP), which worked in identical cycling conditions, were used. The allele frequencies were 0.809 for HPA-1a, 0.191 for HPA-1b, 0.891 for HPA-2a, 0.109 for HPA-2b, 0.591 for HPA-3a, 0.407 for HPA-3b, 0.997 for HPA-4a, 0.00 for HPA-4b, 0.934 for HPA-5a and 0.066 for HPA-5b. When compared to results of studies of various other Caucasian populations, our population displayed a slightly but not significantly higher proportion of the HPA-1b and 2b alleles.

Antigens, Human Platelet↗
PubMed1993

Permissible mismatches, acceptable mismatches, and tolerance: new trends in decision making.

The identification of permissible mismatches that do not impair graft survival might open exciting new possibilities which we should follow up. The data are preliminary, but if true, 50% of the patients in Eurotransplant could get a kidney with optimal graft survival. For sensitized patients we might consider adding a CTLp test, with and without CsA, to our serological crossmatch tests. This might be beneficial especially for interpreting noncurrent crossmatches. Information on the activation status of the donor-specific cytotoxic T cells on the day of transplantation (primed or not, CsA-resistant or not) provides additional information which could facilitate the decision of whether or not to accept a mismatched graft, even in case of donor-specific antibodies in historical sera. Under certain circumstances, haplotype-shared blood transfusions can induce transplantation tolerance. Time will tell whether the determination of the level of donor-derived soluble HLA antigens might be helpful in an early diagnosis of rejection. It might become a new device to monitor homograft reactivity and to identify the patients in whom immunosuppression could be decreased or even discontinued.

Blood Transfusion↗
PubMed1992

Quantitation of the human component C4: definition of C4 Q0 alleles and C4A duplications.

We determined the C4 plasma concentrations of 48 genotypically CA4- and C4B-defined unrelated individuals from 34 families with a total of 196 members by an enzyme-linked immunosorbent assay using Rg:1,2 (C4A) and Ch:1 (C4B) specific monoclonal antibodies. The results obtained allowed the establishment of rules for the detection of C4 Q0 alleles in the heterozygous form and of C4A gene duplications. In the present study seven homoduplications of the C4A 3 allotype were defined which had not been detected by allotyping. This procedure allows the simple, reliable, and quick determination of Rg:1,2 and Ch:1 plasma levels which are not influenced by daily rhythms of C4 production.

Alleles↗
PubMed1990

Heterogeneity in protein patterns of CGL blast crisis cells: discrimination between lymphatic and myeloic lineages.

Studies on cell-membrane-bound proteins in the human hematopoetic system revealed that the expression of certain peptides is restricted to the differentiation lineage. We applied discontinuous polyacrylamide gel electrophoresis of triton X-114 lysates to identify such proteins for a new diagnostic approach in human leukemia. A polypeptide with an apparent molecular mass range of 24 kd (p24) was found predominantly in cells of chronic granulocytic leukemia (CGL), myeloic type of blast crisis, and normal granulocytes. The data presented here suggest a role of this protein in the biology of malignant cells in chronic granulocytic leukemia throughout the course of the disease.

Biomarkers, Tumor↗
PubMed1990

Systemic lupus erythematosus in dogs: association to the major histocompatibility complex class I antigen DLA-A7.

The DLA-A,B antigens and the allotypes of the fourth complement component have been determined in German shepherd dogs suffering from systemic lupus erythematosus. We have typed 26 unrelated affected dogs, 11 animals of a three generation family, and 16 dogs of a colony with a high frequency of the disease. The results obtained from the 26 unrelated diseased dogs were compared to those determined in the 23 unaffected German shepherds. The antigen DLA-A7 was found to be predominant in the diseased group with a c2 = 11.02, Pc = 0.02, and a relative risk for the carriers of 11.93. The antigens DLA-A1 and DLA-B5 were negatively associated to the disease (c2 = 14.95, Pc = 0.001, and c2 = 17.16, P = 0.0008 respectively) and thus may be of protective nature. These data were further substantiated by the typing of the three generation family and the colony.

Animals↗
PubMed1990

Antigens of the major histocompatibility complex in patients with chronic discoid lupus erythematosus.

The frequencies of the major histocompatibility complex class I, class II and class III antigens were determined in 130 patients (88 women and 42 men) with chronic discoid lupus erythematosus, and compared with those of 764 healthy controls. A significant increase in HLA-B7 (38.0% in the patients vs. 25.8% in the control group), HLA-B8 (29.5% vs. 17.4%), HLA-Cw7 (58.9% vs. 26.1%), HLA-DR2 (46.9% vs. 29.7%), HLA-DR3 (32.0% vs. 19.4%), HLA-DQw1 (76.6% vs. 60.5%), and a decrease in HLA-A2 (41.9% vs. 55.7%) was found. The calculated relative risk values for the respective antigens markedly increased when two or more antigens were present in one patient, with a maximum relative risk value of 7.4 for the combinations of HLA-Cw7, DR3, DQw1 and HLA-B7, Cw7 and DR3, which were found in 17.2% of the patients and in only 2.3% of the controls.

Chronic Disease↗
PubMed1990

Modulation of CALLA (CD10) antigen on cultured ALL (REH) cells: effect of various modulators.

Phorbol ester (TPA)-induced down-regulation of the common ALL (CALLA) antigen was studied by continuous flow immunocytometry with the aid of several CD10 monoclonal antibodies, including a new CD10 monoclonal antibody (DGH-10-1-A9), shown to be of IgG1 isotype, recognizing a 100 kDa cell surface protein and effectively inhibited by a series of reference CD10 monoclonal antibodies. The TPA-induced down-regulation of CALLA on REH cells was demonstrated with the aid of the following CD10 monoclonal antibodies: J-5, VIL-A1 and DGH-10-1-A9. No major modulations in cell surface expression of CALLA on REH cells were observed after induction with 1,25-(OH)2 vitamin D3, retinoic acid, recombinant interferon (IFN) alpha 2a and recombinant interleukin 2.

Antibodies, Monoclonal↗
PubMed1989

Quantification of soluble HLA class I gene products by an enzyme linked immunosorbent assay.

A simplified enzyme linked immunosorbent assay utilizing an HLA class I framework-specific monoclonal antibody and a polyclonal enzyme linked beta-2 microglobulin specific antiserum has been established for the quantitative measurement of soluble HLA class I molecules. A total of 219 unrelated healthy individuals and 137 members of 28 families typed for HLA were analyzed for their non-membrane bound, i.e. soluble HLA-A,B,C antigens (sHLA-A,B,C). As reported by others, we observed associations of higher or lower sHLA-A,B,C values to particular HLA antigens: High plasma values were observed in probands positive for HLA-A23, A24, A29, Aw33, Bw65, and Cw8 and low values in HLA-B27 and B37 positive individuals. However, as shown by family studies, levels of sHLA-A,B,C were apparently not controlled by the MHC haplotypes alone, since no significant difference between HLA identical siblings and two haplotype different individuals could be detected. Thus, additional non-MHC linked gene(s) may be involved in the release of class I gene products.

Antibodies, Monoclonal↗
PubMed1989

HLA class I biochemistry: definition and frequency determination of subtypes by one-dimensional isoelectric focusing and immunoblotting.

Previous biochemical studies of HLA class I gene products were based on the use of radiolabelled lymphoblastoid cell lines and/or mitogen-stimulated peripheral blood lymphocytes (PBL). We present here a nonradioactive methodology for defining HLA class I polymorphism on a small number of cells, such as 5 x 10(6) lymphocytes, the vitality of which is not a requirement in contrast to radiolabelling techniques, where 1-2 x 10(6) PBL are needed. We analyzed 54 serologically typed families with a total of 261 individuals and 214 haplotypes by one-dimensional isoelectric focusing and subsequent immunoblotting, using a polyclonal anti-class I heavy chain serum. The banding patterns segregated within families and correlated with the serological results. A substantial number of HLA-A and HLA-B products appeared biochemically heterogeneous allowing the definition of subtypes and the calculation of their frequencies.

Alleles↗
PubMed1989

Typing for HLA class I gene products using plasma as source.

Soluble HLA class I proteins have been found in serum or plasma of healthy and diseased individuals. Here we present evidence that these molecules can be readily used for determination of the HLA type by biochemical methods. Immunoprecipitation of the soluble class I gene products using monomorphic monoclonal antibodies coated to immunobeads and one-dimensional isoelectric focusing followed by immunoblotting represents a feasible and reproducible technique for typing. Analysis of these gene products in families (n = 12, with a total of 62 individuals) as well as in the population (n = 82) showed that all serologically defined antigens tested to date were present in plasma. A reference chart established primarily for the membrane-bound antigens could also be used for the soluble ones.

Blood Proteins↗
PubMed1989

Allotyping for HLA class I using plasma as antigen source.

Immunoadsorption of soluble HLA class I antigens onto immunobeads, one-dimensional iso-electric focusing of these proteins and subsequent immunoblotting allows a biochemical identification of HLA class I allotypes. The distinct protein bands can be clearly attributed to particular HLA antigens and are comparable to those observed after detergent solubilization of membrane-bound HLA antigens. Segregation analysis showed that the biochemically detected pattern of soluble class I gene products followed Mendelian inheritance. However, antigens such as HLA-A1, -A2, -B8, and -B51 were not always clearly detectable, a phenomenon attributable to either different plasma concentrations of these HLA antigens or variable affinity of the monoclonal antibody used to capture class I antigens. These results show that in principle allotyping of HLA class I using plasma as the antigen source is feasible, but with the limitation that some antigens may not be easily detected in some individuals.

Histocompatibility Antigens Class I↗
PubMed1989

Biochemical evidence that the DLA-B locus codes for a class II determinant expressed on all canine peripheral blood lymphocytes.

We have analyzed the products of the canine DLA-B gene locus by biochemical and serological methods. Due to its ubiquitous expression on lymphocytes this antigen series was thought to be of class I nature. However, by two-dimensional gel electrophoresis and lysostrip experiments we could unequivocally identify the DLA-B antigens as typical class II gene products. The serological polymorphism is caused by the beta-chain, whereas the alpha-chain appears invariant. The presence of these class II gene products on almost all lymphocytes in the dog is in sharp contrast to the numerous reports on their restricted expression in other mammalia such as man and mouse.

Animals↗
PubMed1989

Relevance of complotyping and subtyping of MHC class I gene products in haplotype definition for allogeneic bone marrow transplantation.

In preparation for a bone marrow transplantation 217 patients and their families were complotyped for Bf, C4A and C4B in addition to the routinely performed HLA-A,B,C,DR and HLA-D typing. In 147 families uncertainties in haplotype definition occurred which could be solved in 37 cases (25%) by complotyping. Additionally, patients and their relatives were subtyped for class I gene products by one-dimensional isoelectric focusing, a method by which serologically identical HLA-A, B, or C antigens could be split in five out of 22 cases tested. The results obtained clearly show the relevance of both methodologies for finding the best match of donor/recipient pairs to help to prevent MHC-induced graft-versus-host disease after bone marrow transplantation.

Bone Marrow Transplantation↗
PubMed1988

Treatment of acute graft-versus-host disease after HLA-partially matched marrow transplantation with a monoclonal antibody (BMA031) against the T cell receptor. First results of a phase-I/II trial.

As part of an ongoing phase-I/II trial, 2 patients received a 5-day treatment course with a murine monoclonal antibody (MAB) directed against the human T cell receptor (BMA031) as primary therapy of acute grade III skin and gastro-intestinal graft-versus-host disease (GvHD) occurring after allogeneic bone marrow transplantation (BMT). All MAB infusions were tolerated without side effects. A complete response of all symptoms of acute GvHD could be attained by MAB therapy under a continued baseline immunosuppression with cyclosporin (CSP), and both patients remain alive and disease-free at 7 and 8 months after therapy without evidence of chronic GvHD. Although the exact treatment scheme has still to be defined, we conclude that this MAB may be useful as primary therapy of acute GvHD. However, the potential hazards of 'in vivo' therapy with MABs directed against T lymphocytes call for a critical evaluation of this treatment modality.

Adult↗