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Biomedical subjects

S Seidl

Publications and source records attributed to S Seidl.

At least 19 recordsLinked to original sources

Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population.

The Epstein-Barr virus (EBV) has been classically associated with nasopharyngeal carcinoma and Burkitt's lymphoma, a monoclonal B-cell non-Hodgkin's lymphoma. Since the EBV genome has also been found in post-transplant lymphomas and lymphomas arising in individuals infected with the human immunodeficiency virus, evidence has now accumulated that EBV might be the initiator of a multi-step process leading from polyclonal B-cell hyperplasias to monoclonal lymphoma. In a retrospective study of 60 T-cell lymphomas of various types, we found EBV DNA in 21 (35%) using Southern- and/or dot-blot techniques. Eight of 14 nodal samples of angio-immunoblastic lymphadenopathy (57%) were shown to harbour detectable EBV DNA. The tumour with the next highest frequency, 47% (7/15 cases analyzed) was pleomorphic T-cell lymphoma, medium- and large-cell type; EBV was found both in nodal and in extranodal lymphomas of this type. Lymphoepitheloid (Lennert's) lymphoma and large-cell anaplastic lymphoma were positive in 2/5 and 3/8, respectively, of the cases analyzed. No viral DNA could be demonstrated in 3 T-immunoblastic and 5 T-lymphoblastic lymphomas. Clonotypic analysis revealed monoclonal as well as oligoclonal virus populations. Our data suggest that, at least in some of these entities, the presence of the EBV genome might be due to secondary mechanisms such as escape from immune surveillance.

DNA, Viral

HLA-DRB3 gene alleles in Caucasian patients with Graves' disease.

Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P < 0.001). HLA-DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P < 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P < 0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P < 0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes.

Alleles

Abbott HCV EIA 2nd generation: a new screening assay.

An enzyme immunoassay for the detection of antibodies against structural and nonstructural domains of the hepatitis C virus (EIA-2) was compared to a first generation test (EIA-1) that can only detect antibodies against one nonstructural antigen (c100). EIA-2 revealed elevated detection rates as assessed in high risk and patient populations as well as lower repeat reactive rates in volunteer blood donors. Research test systems proved an increase in apparent specificity.

Blood Donors

[Gene amplification with PCR and sequence specific HLA oligonucleotide typing].

Genetic polymorphism in the HLA class II region has been identified by the analysis of the polymerase chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant typing kit enables HLA typing independent of gene expression and quality of lymphocytes. One of the advantages of this technique is that the definition of splits is much better than typing by serology.

Base Sequence

[Development of HLA antibodies in thrombocyte substitution with cell separator products].

In a retrospective study we investigated the development of HLA antibodies in patients who received platelet concentrates from cell separators. 118 hematological/oncological patients from the Frankfurt University Clinics were investigated. They received between 4 and 66 platelet concentrates for the duration of 30 months. All patients had a negative antibody screening on admission. 31% developed either transient (15%) or permanent (16%) lymphocytotoxic antibodies. The increasing number of platelet transfusions did not correlate with the development of HLA antibodies, but the appearance of these antibodies seemed to be dependent on the disease. Permanent antibodies appeared in 8% of patients with acute leukemia, whereas 38% of patients suffering from CL, lymphoma, MDS and myeloma produced antibodies. Some patients (18) received granulocyte transfusions as well. It is striking that 11% of these patients developed permanent and 28% transient HLA antibodies. There exist no data about recent transfusions or previous pregnancies. To lower the rate of sensitization in patients with diseases such as CL, lymphoma, MDS and myeloma, it should be discussed whether leukocyte-depleted platelet concentrates should be given to these patients.

Blood Component Transfusion

[Decreasing the risk of post-transfusion non-A, non-B hepatitis by anti-HCV screening].

In May 1990 a specific enzyme immunoassay (EIA) for NANBH was developed by recombinant DNA technology which detects antibodies to a virus called hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho Diagnostic Systems with recombinant antigens from Chiron Corp. based on extraction from high infectious titer chimpanzee plasma RNA after transcription into cDNA. We tested the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated anti-HCV-positive blood donors and 8.2% anti-HCV-positive hemodialysis patients.

Blood Donors

[Prevention of post-transfusion non-A, non-B hepatitis by anti-HCV screening].

Since May 1990 a specific enzyme immunoassay (EIA) for NANBH has been developed by recombinant DNA technology which detects antibodies to a virus called hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho-Diagnostic Systems with recombinant antigens from Chiron Corp. based on extraction from high infectious titre chimpanzee plasma RNA after transcription into cDNA. We tested the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated anti-HCV positive blood donors and 8.2% anti-HCV positive hemodialysis patients.

Antigens, Viral

[Gene amplification with PCR and sequence-specific HLA oligotyping].

Genetic polymorphism in the HLA-class II region has been identified by the analysis of the polymerase-chain reaction (PCR) products using sequence-specific oligonucleotide (SSO). The PCR-SSO method permits precise and direct analysis of allelic variations with as little as 1 microgram of genomic DNA. The standardized, uniform hybridization and critical wash protocol of the Eurotransplant-typing kit [2] enables HLA-typing independent of gene expression and lymphocytes quality. One of the advantages of this technique is that the definition of subtypes is much better than is typing by serology.

Amino Acid Sequence

The HLA-DQ beta non-Asp-57 allele: a predictor of future insulin-dependent diabetes mellitus in patients with autoimmune Addison's disease.

HLA-DR specificities in 72 Addison's (AD) patients and 808 local controls were compared. We confirmed earlier reports that the HLA-DR3 specificity is significantly increased in AD patients. In our study a relative risk of 3.4 chi 2 = 22.5; pc = 0.01) for the disease was calculated. Analysis of HLA-DQB1 alleles in DR4+ Addison's patients with diabetes mellitus (N = 6) and without IDDM (14 of 18 individuals tested) revealed that the HLA-DQw8 allele (DQB1*0302) was significantly increased in AD patients with IDDM (chi 2 = 13.5; p = 0.001); conversely, a clustering of the HLA-DQw7 allele was detected in DR4+ Addison's patients without IDDM. We thus conclude that particular polymorphic alleles corresponding to non-charged amino acids at position 57 of the HLA-DQ beta-chain [non-Asp-57 alleles] are associated with IDDM also in Addison's patients.

Addison Disease

The in vitro and in vivo evaluation of whole blood and red cell concentrates drawn on CPDA-1 and stored in a non-DEHP plasticized PVC container.

A new polyvinyl chloride (PVC) blood storage container, PL 2209, plasticized with butyryl-n-trihexyl-citrate (BTHC) instead of diethylhexyl phthalate (DEHP) was used for in vitro and in vivo studies. Whole blood and red cell concentrates drawn on CPDA-1 were stored 42 days at 1-6 degrees C. Various biochemical parameters were tested and compared to those values seen in the literature for products stored in DEHP-plasticized containers. Measurements of lactate production, glucose consumption, sodium and potassium ions for both whole blood and red cells were compatible with published data. Adenosine triphosphate (ATP) values were on the average 73% for the red cell units and 80% for the whole blood units after 35 days storage. Hemolysis was 0.43% for the red cell concentrate and 0.38% for the whole blood units after the same storage period. Autologous recovery studies after 35 days of storage for both the whole blood units and red cell concentrate gave 80% recovery 24 h after reinjection. From these data it can be concluded that PL 2209 BTHC-plasticized PVC blood storage containers allow 35 days storage of blood draw on CPDA-1 and can be considered as an alternative to DEHP-plasticized PVC containers.

Adenine

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Adolescent

[Search for bone marrow donors for patients with hematologic-oncologic diseases].

In recent years, bone marrow transplantation (BMT) has been used as a curative treatment for patients with intractable hematopoietic disorders, such as leukemia. However, lacking other options, only 30 percent of patients will have an HLA-identical family-member bone marrow donor. For patients without HLA-identical family members, HLA-identical, MLC non-reactive unrelated donors have been used. However it is very difficult to find HLA-compatible donors from an unrelated donor registry, due to the highly polymorphic HLA-system. Therefore, we need approximately 6-12 months to find an HLA-matched donor who would agree to donate bone marrow.

Bone Marrow Transplantation

[Hepatitis C virus antibodies (HCV) in patients treated with chronic hemodialysis].

Patients undergoing chronic hemodialysis are frequently affected by nosocomial viral infections, as indicated by the high prevalence of HBV antibodies. The question, to what extent HCV is transmitted by blood transfusions (NANB-PTH), or acquired in a nosocomial manner, is still unanswered. We therefore evaluated the HCV antibody rate of 387 sera of dialysis patients on the "Eurotransplant" waiting list. The HCV antibody reactivity ranged from 5.4 to 12.0% between different dialysis centers. In highly immunized (HLA antibody positive) long-term dialysis patients 31.3% (vs. 8.3% in non-immunized patients) were HCV antibody positive.

Antibodies, Viral

[Immune hematologic diagnosis in women with habitual abortion].

It has been proposed that unexplained recurrent miscarriages are caused by maternal immune rejection of the semi-allogenic fetus. The problem has been treated by immunization with paternal leukocytes to induce maternal antipaternal-antibodies that may block immune rejection of the fetus. It has been suggested that excessive sharing of HLA antigens predisposes couples to recurrent abortion. However, we did not find evidence for excessive HLA-sharing. The degree of sharing did not differ significantly between the couples with recurrent miscarriages and controls with successful pregnancies.

Abortion, Habitual