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Biomedical subjects

E Albert

Publications and source records attributed to E Albert.

At least 73 records · Page 4Linked to original sources

Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes.

We have investigated the extent of DNA variability in intronic simple (gt)n(ga)m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)n(ga)m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.

Amino Acid Sequence↗

Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals.

We derived a total of 146 T lymphocyte lines specific for human myelin basic protein (MBP) from the peripheral blood of 20 MS patients and from a control group of 12 healthy donors, and determined the reactivities of T cell lines by [3H]thymidine incorporation on exposure to MBP and MBP peptides 1-44, 45-89, and 90-170. We defined HLA restriction of the T lines by using monoclonal antibodies against monomorphic determinants on human HLA-DR, HLA-DQ, and HLA-DP molecules. MBP-specific T cell lines could be isolated with a comparable efficiency from MS patients and healthy individuals. In both groups, MBP-specific T lymphocytes recognized at least 4 different epitopes in the MBP molecule, and specificities showed comparable patterns for different MBP peptides. MBP-specific T cell lines derived from MS patients and controls were restricted by DR products of the human major histocompatibility class II locus. Notable phenotypic differences of T cell lines existed between the 2 groups. Lines isolated from MS patients expressed predominantly the CD3+ CD4+ CD8- phenotype, while some control lines were composed of up to 87% CD3+CD4+CD8+ T lymphocytes. These findings illustrate the presence of MBP-specific T cells in MS patients and controls that are similarly sensitized to MBP and restricted by HLA-DR products.

Adult↗

Addison's disease and pregnancy.

Five case reports are presented illustrating that pregnancy and Addison's disease are not incompatible, provided adequate substitution therapy is given.

Addison Disease↗

Thymus in myasthenia gravis. Isolation of T-lymphocyte lines specific for the nicotinic acetylcholine receptor from thymuses of myasthenic patients.

The thymus is believed to play a central role in the pathogenesis of Myasthenia gravis (MG). According to a previous hypothesis, MG is initiated within the thymus by immunogenic presentation of locally produced nicotinic acetylcholine receptor (AChR) to potentially autoimmune T cells. Data of 10 consecutive MG patients demonstrate two critical features of MG thymuses that support the concept of intrathymic activation of autoreactive, AChR-specific lymphocytes. Morphologically, the thymuses showed lympho-follicular hyperplasia in nine cases and benign thymoma in one case. The paramount feature revealed by immunohistological double marker analyses was the intimate association of myoid cells (antigen producing) with interdigitating reticulum cells (potentially antigen presenting cells), both of which were surrounded by T3+ lymphocytes in thymus medulla. All 10 thymuses contained T lymphocytes reactive with AChR. This was in contrast to the peripheral immune compartment (blood) where in only 3 of 10 patients, significant T cell responses to AChR were observed. AChR-specific T cell lines could be established from 8 of 10 thymuses, all members of the helper/inducer subset as indicated by the expression of markers T3 and T4.

Adolescent↗

Renal transplantation at the Munich Transplant Center: a retrospective single-center review.

The use of different immunosuppressive protocols (high-dose/low-dose CsA) has little effect on first cadaveric transplants in nonsensitized patients. However, low-dose CsA induction treatment reduces early nephrotoxic crises. There is a clear benefit of quadruple drug induction treatment for retransplants and sensitized transplant candidates. Steroid-free immunosuppressive therapy can be applied to a majority of long-term patients.

Cyclosporins↗

On organically based hallucinatory-delusional psychoses.

In an investigation of 70 chronically mentally ill patients in a district psychiatric hospital, 11 cases were discovered which had been diagnosed up to now as schizophrenia, but could now be diagnosed as being of organic origin. In group 1 (cases 1-6) there are dementive states after toxic, inflammatory or early childhood brain damage and familial epileptic malady with slowly progressive brain atrophy. They were easy to recognize clinically in their organic psychosyndromes, dementia, neurological symptoms and CT findings showing extensive, massive brain damage. In group 2 (cases 7-11), in contrast, there are patients with chronic psychoses of remittent course, with brain findings indicative of centrencephalic damage. On superficial examination they give a schizophrenic picture, but can be differentiated from this by the absence of schizophrenic personality changes and thought disturbances, and also by the form of the hallucinations. These are distinguished by their plastic character, and show the criteria which Schröder had already pointed out 60 years ago for the differentiation of exogenous and endogenous hallucinations.

Aged↗

Immunogenetics of juvenile chronic arthritis.

The current knowledge of the relationship between the HLA system and the different forms of Juvenile Chronic Arthritis is reviewed: Of the different forms the Early Onset Pauciarticular JCA is associated with DRw8, DR5 and A2, the Polyarticular Onset Rheumatoid Factor positive JCA shows the same pattern of association as does the Adult Rheumatoid Arthritis namely with DR4 and DR1. Juvenile Spondylitis is strongly related to the presence of B27. For the other clinical forms of Juvenile Chronic arthritis the data are not sufficiently well established to give a definite association. In Early Onset Pauciarticular JCA the association with the DR antigens DRw8 and DR5 is independent of that with HLA-A2. Thus there must be at least two HLA linked regions contributing to susceptibility to this form of JCA, one in the region of HLA-A and the other one in the HLA-DR region. If Early Onset Pauciarticular JCA is analysed according to the type of onset (Monoarticular, with large joints, with large and small joints, with small joints only and with Iridocyclitis) there are no significant differences in the frequencies for the associated DR alleles DR5 and DRw8. The antigen DR4 is not found at all in patients with Monoarticular Onset and in increasing frequencies with the increased number of involved joints. Analysis of the same patients according to the clinical course of the disease (Persistent Pauciarticular, Extended Pauciarticular, Polyarticular) shows that again there are no significant deviations for the associated antigens A2, DR5, DRw8. DR4 is not found in the group with Persistent Pauciarticular Disease.

Adolescent↗

[Personality change following encephalitis lethargica in childhood. Eventual fate of a patient].

An account is given of a patient who died at the age of sixty. He had no recollection of having had encephalitis as a child. In his schooldays, the patient was subject to severe behavioral disorders which were not susceptible to outside influence. During his military service he was frequently punished for conduct prejudicial to discipline and good order, and at the front he was even sentenced to death, but reprieved. His later life brought him no tranquility, ever new conflicts driving him from one job after another. Breaking into uncontrollable fits of rage, he would psychically attack the people around him, threatening to kill them. He was incapable of controlling his impulses. He spent the second half of his life in institutional care, his extrems impulsiveness being the cause of considerable disruption. Post mortem examination confirmed the encephalitis lethargica he was assumed to have suffered as a child, which was responsible for the typical change of character. It is evident how encephalitis lethargica in childhood sets a lifelong mark on the conduct, with appalling consequences.

Alzheimer Disease↗

Association of progressive systemic scleroderma to several HLA-B and HLA-DR alleles.

The HLA-A, B, C, and DR loci of 136 patients with progressive systemic scleroderma have been determined. The patients were classified according to the extent of their skin affection and into groups with or without immunologic and inflammatory signs of the disease. The antigens of the A locus did not show any significant deviations in frequency of occurrence. An increase of HLA-B8 and HLA-DR3 was only proved in the male patient group. Furthermore, in the HLA-DR gene locus, an increase in frequency of HLA-DR1, 2, 3, and 5 could be found. However, in the total set of patients, only the correlation of HLA-DR5 with progressive systemic scleroderma reached significance. Patients suffering from the CREST (calcinosis, Raynaud's phenomenon, esophagus, sclerodactyly, and telangiectasia) syndrome showed an increase of HLA-DR1. Patients with inflammatory signs of the scleroderma showed an accumulation of HLA-DR2. Several HLA-linked genes control the susceptibility to scleroderma.

Adult↗

Neopterin release in human mixed lymphocyte culture: requirement of HLA-DR disparity.

Recent evidence suggests that immune responses in vivo as well as in vitro are accompanied by release of neopterin [C. H. Huber, et al. (1983) J. Immunol. 130, 1047]. This investigation aimed to elucidate the genetic control of in vitro neopterin release in family mixed lymphocyte culture (MLC) studies. Neopterin levels and responder cell proliferation were assessed in a total of 92 MLCs established from different intrafamilial combinations. Results indicated a strong association between the magnitude of responder cell proliferation and the neopterin levels induced by stimulation with allogeneic cells. This conclusion was based on three findings: first, almost no neopterin release and proliferation was seen in MLCs established between HLA genotypically identical siblings; secondly, very low proliferation and neopterin levels were observed in MLCs between HLA-DR phenotypically identical family members; and thirdly, high neopterin release and strong cellular proliferation were a feature of MLCs established between individuals differing for at least one HLA-DR antigen. We thus conclude that T cell activation subsequent to recognition of HLA-DR disparity represents an essential prerequisite for induction of neopterin release in human MLC.

Biopterins↗