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Biomedical subjects

J D'Amaro

Publications and source records attributed to J D'Amaro.

At least 19 recordsLinked to original sources
PubMed1992

Possible relation between HLA and ABO type and prognosis of uveal melanoma.

Not only local parameters but also genetic determinants like the HLA genes may play a role in the development and clinical behavior of malignant tumors. In skin melanoma the presence of HLA-B40 is associated with a poor prognosis. We tested the hypothesis that the clinical behavior of uveal melanoma is influenced by the HLA type of the patient. The HLA types of 44 patients with uveal melanoma had been determined before operation with a view to using the cornea of the enucleated eye for an HLA-matched corneal transplantation. We compared the ABO and HLA types of the patients with the development of metastases and with the ten-year patient survival. An association was observed between the presence of HLA-B40 and death due to metastasis of uveal melanoma. We conclude that the HLA type of the patient may influence the clinical behavior not only of skin melanoma but also of uveal melanoma.

ABO Blood-Group System↗
PubMed1992

Immunogenetics of human minor histocompatibility antigens: their polymorphism and immunodominance.

Minor Histocompatibility (mH) antigens are polymorphic endogenously synthesized products that can be recognized by alloreactive T cells in the context of major histocompatibility complex molecules. In transplant situations where tissue donor and recipient are matched for HLA, mH antigens may trigger strong cellular immune responses. To gain insight into the polymorphism of mH antigens we studied their frequencies in the healthy population. Five HLA class I restricted mH antigens recognized by distinct cytotoxic T-cell (CTL) clones were used in the population genetic analysis consisting of a panel (N = 100) of HLA typed target cells. Three mH antigens showed phenotype frequencies of 69% or higher, this contrasted the frequencies of two other mH antigens with 16 and 7% respectively. To gain insight into the "functional" polymorphism of the T-cell response to mH antigens, we analyzed the specificity of CTL clones within individuals. Three out of five individuals investigated shared a CTL response to one single HLA-A2 restricted mH antigen. These results indicate limited allelic polymorphism for some mH antigens in the healthy population and are suggestive of the existence of immunodominant human mH antigens.

Alleles↗
PubMed1992

Relative contribution of HLA-DQA and -DQB alleles to predisposition to insulin-dependent diabetes mellitus.

The presence of DQA and DQB alleles conferring protection or susceptibility was assessed in a panel of 39 insulin-dependent diabetes mellitus patients and 39 healthy control subjects from the central highland of Ethiopia. The results were grouped into three entities: a combination of alleles conferring susceptibility, a group conferring protection, and a group without any apparent HLA-DQ or -DR predisposition to insulin-dependent (type 1) diabetes mellitus (IDDM). Statistical analysis revealed that the relative risk of the first group is 64.1. If a similar approach is applied to the data on a study in caucasoid IDDM patients and controls of Kahlil and colleagues, the pattern is fully consistent with the data presented here, with an extraordinarily high relative risk (RR 258.2). It will be of interest to study whether this subdivision is reflected or supported by clinical or etiologic differences of the disease. The predictive value of susceptibility phenotypes appears to be more accurate by the proposed subdivision. Furthermore, in combination with islet-cell antibody analysis, assessment of genotype will permit more accurate identification of prediabetic individuals to be entered in clinical trials.

Alleles↗
PubMed1992

A personal computer program for large-scale comparisons of related nucleotide sequences.

A personal computer program (COMPSEQ) has been developed which can present an informative listing of pre-aligned exonic nucleotide sequences and of their translations to amino acid sequences as well run triplet-oriented analyses on these sequences in a given reading frame. The sequence listing focuses on the differences between related sequences by suppressing the concordances between them.

Algorithms↗
PubMed1992

Transfusion results of filtered and subsequently stored random platelet suspensions prepared from buffy coats.

There is almost general agreement that removal of leukocytes from blood components reduces the incidence of HLA-antibody formation and refractoriness to random platelet transfusions. Recently filters have become available, which are able to reduce leukocyte contamination in platelet suspensions with acceptable platelet loss. We evaluated a cellulose acetate (CA) and a polyester (PE) filter, and stored buffy coat-derived platelet suspensions after filtration. Both filters are effective for the removal of leukocytes to levels below 5 x 10(6) per transfusate. For the CA filter, platelet recovery was 73 +/- 13% yielding 256 +/- 53 x 10(9) platelets per transfusate from 6 donors. For the PE filter, platelet recovery was 90 +/- 9% and 327 +/- 51 x 10(9) platelets per transfusate. When a loading dose of less than 5 x 10(8) leukocytes was applied, 98% of the CA-filtered suspensions and 100% of the PE-filtered suspensions contained less than 5 x 10(6) residual leucocytes. In 123 patients transfusion results of CA-filtered platelet suspensions stored for 72 h, were compared with those obtained by non-stored, non filtered, random platelet suspensions which had been leukocyte depleted by differential centrifugation. Platelet increments 1 and 20 h after transfusion showed no statistical difference between CA-filtered platelet transfusions stored for 72 h and non-stored, non-filtered platelet transfusions. In a new cohort of 117 patients, two filters and various postfiltration storage times were compared. Using both filters, the 1-hour posttransfusion increments decreased to approximately 60% after 96 h of storage compared to results of storage periods of 72 h or less.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding Time↗
PubMed1992

No direct clinical relevance of the human leucocyte antigen (HLA) system in clozapine-induced agranulocytosis.

The clinical use of clozapine in psychiatry is restricted by the associated risk of agranulocytosis. This risk is significantly higher than that associated with conventional antipsychotic medications. In order to identify a possible parameter to detect susceptible individuals before treatment, 103 patients with a history of clozapine-induced granulocytopenia or agranulocytosis and 95 matched control patients were typed for human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and for a number of neutrophil-specific alloantigens. No significant association between certain HLA alleles or neutrophil antigens and susceptibility to clozapine-induced granulocytopenia or agranulocytosis was observed.

Agranulocytosis↗
PubMed1991

Association of HLA-DR4 with a more progressive disease course in patients with rheumatoid arthritis. Results of a followup study.

The association between HLA-DR antigens and rheumatoid arthritis (RA) was investigated in a well-characterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA-DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA-DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4-negative RA patients, DR4-positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second-line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second-line drugs was higher in DR4-positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA.

Adult↗
PubMed1991

Positive correlation between oligonucleotide typing and T-cell recognition of HLA-DP molecules.

The identification of 19 different HLA-DPB1 sequences implicates the existence of more DP specificities than can be typed for with cellular methods. How many of the DP beta sequences can be specifically recognized by T cells, and which of the polymorphic regions can contribute to the specificity of allorecognition, is not known. In order to investigate the distribution and the immunological relevance of recently described DPB1 alleles, we have typed a panel of 98 randomly selected Dutch Caucasoid donors for the HLA-DPB1 locus by oligonucleotide typing. Comparison of the typing results with primed lymphocyte typing (PLT) defined DP specificities shows an extremely good correlation. Moreover, additional alleles could be defined by oligonucleotide typing reducing the number of DP blanks in the panel. By selecting the appropriate responder stimulator combinations we were able to show that distinctive PLT reagents against oligonucleotide defined specificities DPB1*0401, DPB1*0402, DPB1*0901, and DPB1*1301 can be generated. To investigate in more detail which part of the DP molecule is responsible for the specificity of T-cell recognition, T-cell clones were generated against HLA-DPw3. The clones were tested for the recognition of stimulators carrying DPB1 alleles which had been defined by oligonucleotide typing and sequence analyses and which differed in a variable degree from DPB1*0301. The recognition patterns demonstrated that differences of one amino acid in polymorphic regions situated either in the beta sheets or alpha helix of the hypothetical model of the HLA class II molecule can eliminate T-cell recognition. Furthermore, sequence analyses revealed a new DPB1 allele designated DPB1*Oos.

Alleles↗
PubMed1991

Longevity and heredity in humans. Association with the human leucocyte antigen phenotype.

Several arguments support the idea of a link between longevity and heredity, both in experimental animals and in the human species. In mice, genes in the major histocompatibility complex (MHC) are associated with a significant effect on life span. Results of analogous studies in man are confusing and contradictory. We have therefore investigated the question of an association of the human leucocyte antigen (HLA) and longevity in a large and ethnically homogeneous population. Our study population consisted of all 964 available inhabitants aged 85 years and over in the Dutch community of Leiden (pop. 104,000). Our control group comprised 2444 young inhabitants, aged 20-35 years, with an identical ethnic and demographic background. In addition, control groups of different age-brackets from the same region were used. Two antigens differed in frequency: HLA-B40 was lower and HLA-DR5 was higher in the group of 85 years and over, as compared to the control group, aged 20-35 years. Both differences were more evident in females. No major disease associations with HLA-B40 or HLA-DR5 have been reported. It is unlikely that these results are a chance observation: the overall similarity of the HLA pattern of the old and young age groups is a confirmation of their identical ethnic and demographic background and the changes as observed in the different age-groups were gradual. The biological meaning of these results is still unclear.

Adult↗
PubMed1991

Corneal graft survival in HLA-A- and HLA-B-matched transplantations in high-risk cases with retrospective review of HLA-DR compatibility.

In 107 HLA-A- and HLA-B-matched corneal transplantations performed in high-risk patients, the 3-year graft survival was 60.5%. The criteria used for the definition of high risk were vascularization of the recipient cornea and/or one or more previous failed grafts; they were also the indications for HLA typing and matching. Donor/recipient compatibility was defined by the presence of only 0 or 1 HLA-A or HLA-B mismatches. When non-immunological factors leading to graft failure were excluded, the 3-year survival was 76.3%. During that follow-up period, a total of 33 grafts failed; in 13 cases, the cause was allograft rejection. When only first transplants were considered, a 3-year graft survival of 81.0% was observed. Retrospective DR typing was possible in 33 cases. Because only three graft rejections occurred in that group, we were unable to assess the importance of DR compatibility on the survival of corneal allografts.

Follow-Up Studies↗
PubMed1990

HLA-DR4 associated response to corticosteroids in Graves' ophthalmopathy patients.

Fifty-seven patients with severe Graves' ophthalmopathy were treated with corticosteroids. Therapeutic outcome was assessed according to predetermined criteria as response (n = 37) or non-response (n = 20) to therapy. Patients were typed for HLA-A, -B, -C, -DR and -DQ. HLA-DR4 was completely absent in the 20 non-responder patients (corrected p value = 0.042). In the responder group 14 of the 37 patients were HLA-DR4 positive. This study shows that in Graves' ophthalmopathy patients the presence of HLA-DR4 is associated with a good response to corticosteroid therapy. The frequency of HLA-DR4 in the Graves' ophthalmopathy population as a whole, however, was not different from normal (25% versus 26%). But as reported previously, the frequency of HLA-DR3 was significantly increased in the Graves' ophthalmopathy patients when compared to healthy blood donors (47% versus 24%, corrected p value = 0.02). No significant deviations were found in the HLA-A, -B, or -C loci.

Adrenal Cortex Hormones↗
PubMed1990

The effect of HLA matching on kidney graft survival in separate posttransplantation intervals.

The effect of matching for the HLA antigens has been well established as important in the prognosis of kidney grafts. By analyzing the effect of matching on first transplants from unrelated donors in specific intervals up to 3 years posttransplantation, we show that the effect of HLA-DR matching is strongest in the first 5 months following transplantation (relative risks of graft failure 1.31 and 1.77 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches). For patients whose grafts remained functioning after 5 months, there was no significant further improvement in graft survival to 3 years (relative risks 1.16 and 0.98 for 1 and 2 HLA-DR mismatches, respectively, compared with no mismatches)--i.e., the gain in graft survival by matching for HLA-DR appears to be due to its influence in the first 5 months following transplantation. For HLA-B, the matching effect was evident both before and after 5 months (relative risks 1.11 and 1.27 for 1 and 2 HLA-B mismatches, respectively, compared with no mismatches and modelled as constant over the 3-year period), whereas no effect of HLA-A matching was evident in the period up to 3 years.

Graft Survival↗
PubMed1990

An unexpected effect of matching for HLA-A9 in renal transplantation.

The observation of elevated levels of HLA class I molecules in sera of HLA-A9-positive individuals, and their potential role in the regulation of the immune response, motivated us to study the effect of the presence of HLA-A9 in either kidney donor or recipient on graft survival. Analysis of data from unrelated first transplants performed within the Eurotransplant area revealed that in the group of patients who were not treated with cyclosporine (n = 2051), transplants with no HLA-DR mismatches in which donors (D) and recipients (R) shared the HLA-A9 antigen (D+R+), had significantly poorer graft survival (P = 0.0001) than all other combinations, reaching a 20% difference at 5 years posttransplantation. This effect, which was not found in the CsA-treated patient group (n = 7297), was specific for HLA-A9. The implications of this findings are discussed in relation to the mechanisms of the alloimmune response.

Cyclosporins↗
PubMed1989

Association of tuberculosis and M. tuberculosis-specific antibody levels with HLA.

In the search for HLA-linked immune response genes that control susceptibility to tuberculosis, we performed HLA typing and measured antibody titers to well-defined Mycobacterium tuberculosis antigenic determinants in 101 patients with sputum smear-positive pulmonary tuberculosis and 64 healthy controls from Surabaya, Indonesia. HLA-DR2 and DQw1 were associated with sputum smear-positive pulmonary tuberculosis (attributable risk = 36% and 39%, respectively), while DQw3 was associated even more strongly with the control group (preventive fraction = 57%). Antibody titers to the TB71 and TB72 epitopes of the 38-kDa protein, present only on tubercle bacilli, were strongly associated with DR2 (Pcorr = .001 and .024, respectively). The association of both the disease and the antibody response to the 38-kDa antigen of M. tuberculosis with Class II HLA genes HLA-DR2 indicates that Ir-gene-mediated regulation of the immune response to this antigen may be of pathogenic significance for the development of sputum smear-positive tuberculosis.

Antibodies, Bacterial↗
PubMed1989

The effect of fresh versus stored blood on post-operative bleeding after coronary bypass surgery: a prospective randomized study.

In a prospective study, 237 patients undergoing a primary coronary bypass operation were randomized to receive 2 units of fresh whole blood (study group) or stored (2-5 d) blood (control group) at the end of the extracorporeal circulation. Serious post-operative bleeding necessitating a re-thoracotomy occurred in 4.2% of all patients with an equal distribution over the two groups. Post-operative haemoglobin content and platelet counts were higher in the study group, but the differences were small and clinically not important. There were no differences in transfusion requirements, post-operative blood losses and haemostatic parameters between the trial groups. At low post-operative platelet counts (below 120 X 10(9) platelets/l) however, patients in the control group lost significantly more blood and had increased transfusion requirements compared with patients in the study group (7.1 versus 4.8 units). These differences must be attributed to qualitative platelet defects in the transfused units of stored blood. The small, clinically insignificant, differences in two laboratory parameters between the study and control groups, and the increased transfusion requirements of a subpopulation of patients with low platelet counts in the control group do not justify giving fresh blood or prophylactic platelet transfusions to coronary bypass patients.

Blood Preservation↗