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Biomedical subjects

H W Kreth

Publications and source records attributed to H W Kreth.

At least 55 records · Page 3Linked to original sources
PubMed1991

Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases.

In order to characterize measles virus (MV) infection in peripheral blood mononuclear cells (PBMCs), RNA was isolated from PBMCs after PHA-stimulation for 72 hr of 9 patients with acute measles, 16 patients with subacute sclerosing panencephalitis (SSPE), 13 patients with various autoimmune diseases, and 16 healthy control donors. The RNA obtained was screened for the presence of MV N (nucleocapsid) gene specific transcripts of either positive or negative orientation in a S1 nuclease protection assay. The sensitivity of this assay allowed us to detect one infected cell in 20,000 PBMCs or 0.1 to 0.05 copies of MV-specific RNA per cell. Using single-stranded DNA or RNA probes expression of MV genomic RNA of negative polarity could be detected in only one case of acute measles and one healthy control donor. Conversely, N-specific transcripts of positive polarity, indicating active transcription, could only be detected in patients with acute measles. In addition, in infected PBMCs and in a persistently MV-infected B cell line positive stranded N-specific transcripts containing leader usually present at very low frequency have been found in relatively increased amounts in comparison with transcripts lacking leader. Whereas the ratio of these RNA species during lytic infection with MV in Vero cells is about 1:50, the ratio found here ranges from 1:3 to 1:10. This altered ratio indicates a specific regulation of MV specific transcription in cells of lymphoid origin that has not been found in any other cell system analyzed.

Animals↗
PubMed1991

Interferon-gamma secretion by in vivo activated cytotoxic T lymphocytes from the blood and cerebrospinal fluid during mumps meningitis.

Functional studies of cerebrospinal fluid T lymphocytes during acute viral infections of the nervous system are rare. Recently, we had the opportunity to investigate the requirements for interferon-gamma (IFN-gamma) production of human in vivo activated (primary) cytotoxic T lymphocytes (CTL) generated during acute viral meningitis. Two HLA-B7-restricted, CD4-, CD8+ CTL clones from cerebrospinal fluid of one patient with mumps meningitis were studied. Although lytic activity was restricted by HLA-B7, the clones produced similar amounts of IFN-gamma when stimulated with HLA-matched and mismatched mumps virus-infected target cells. In addition, peripheral blood mononuclear cells of infected patients secreted significant amounts of IFN-gamma when incubated with autologous or allogeneic (HLA-A/B-mismatched) mumps virus-infected target cells. T cells capable of lytic activity and IFN-gamma secretion could only be isolated from venous blood during the initial phase of the infection. We suggest that the ability of human in vivo activated CTL to secrete INF-gamma early during the course of inflammation and in a HLA-unrestricted fashion is important for the elimination of viruses invading the central nervous system.

Child, Preschool↗
PubMed1991

Epstein-Barr virus-associated lymphoproliferative syndromes: studies in two European families.

The X-linked lymphoproliferative syndrome (XLP), also known as Duncan's disease, is an X-linked recessive disorder that is characterized by the inability of affected individuals to mount a sufficient immune response to Epstein-Barr virus (EBV). After EBV primary infection, male family members suffer from severe infectious mononucleosis (IM), aplastic anemia, hypogammaglobulinemia, and a spectrum of lymphoproliferative diseases. Autosomal mode of inheritance with similar symptoms as in XLP has been reported. We have studied two families with EBV-associated syndromes and an X-linked and an autosomal mode of inheritance, respectively. Affected family members presented with severe IM, hemophagocytosis, aplastic anemia, acquired hypogammaglobulinemia, and B-cell lymphoproliferative diseases.

Agammaglobulinemia↗
PubMed1991

[Epstein-Barr-virus-induced lymphoproliferative diseases].

Infections with EBV are of increasing importance in pediatrics. Molecular and immunological methods have led to important advances in our understanding of the biological properties of this virus and the immunological consequences to its host. EBV-associated lymphoproliferative disorders mainly arise in immunodeficient patients by the unchecked polyclonal outgrowth of EBV-infected B-cells. On the other hand, primary genetic changes in B-cells (chromosomal translocation and oncogene deregulation) may also lead to induction of monoclonal lymphoma.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Tumor suppressor genes: occurrence, significance and function].

Tumor-suppressor-genes were detected by DNA-analysis of childhood tumors. A homozygous deletion or mutation of these genes is closely associated with different malignant tumors. Tumor-suppressor-genes seem to play an important role in cellular development and differentiation. The understanding of this pathomechanism in cancerogenesis is most important for calculating a genetic risk for tumor development.

Biomarkers, Tumor↗
PubMed1991

[Specific gene deletion in patients with cystic fibrosis: pilot study of a small patient cohort].

Identification and molecular cloning of the cystic fibrosis (CF)-gene was a major progress in genetic counseling of families with one or more affected children. In caucasian families about 70% of the CF-patients show a homozygous or heterozygous deletion of one amino acid, that is phenylalanine at position 508 (delta F508). In a pilot study we examined the DNA of 14 CF-patients for F508 deletions. DNA was amplified by PCR and hybridized with a oligonucleotide-probe specific for the mutation containing CF-gene. Surprisingly all of the patients had a deletion of F508 of at least one allele (10 for both alleles, 4 for one allele). This method is of great importance for carrier-diagnosis. The finding of these or other deletions within the CF-gene may represent a prognostic marker for this disease.

Adolescent↗
PubMed1991

[Diagnosis of monozygosity in multiple births by DNA fingerprinting].

The incidence of monozygotic twins is one in 250 pregnancies. Triplets are estimated to occur in 1 of 86(2) pregnancies. Determination of zygosity may be done by comparison of physical characteristics, blood group or tissue typing, chromosome studies, or examination of various other polymorphic protein markers. Here we describe the differentiation between monozygotic and dizygotic twins and triplets by DNA-fingerprinting. This is a fast, non-invasive and reliable (error probability 0.003%) method to determine monozygosity of twins or triplets. It is also a reliable paternity test.

Cesarean Section↗
PubMed1990

[Acquired immunodeficiency].

Secondary immunodeficiencies are much more frequent than primary immunological disorders. There are many etiologies, such as malnutrition, cytostatic drug therapy, burns, protein-losing conditions and infections. This review briefly considers the history of virus-induced immunosuppression. Today, measles and AIDS are the most important virus-induced immunodeficiency diseases. In rate instances, infections with Epstein-Barr virus can lead to hypogammaglobulinemia and B cell lymphomas. A viral etiology should always be considered in all cases of congenital and postnatally acquired immunological disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Epstein-Barr virus infection rapidly progressing to monoclonal lymphoproliferative disease in a child with selective immunodeficiency.

We report on a 30-month-old previously healthy Turkish boy who presented with fever, hepatosplenomegaly and generalized lymphadenopathy. He died 4 months after admission in spite of treatment with steroids, acycloguanosine and cyclophosphamide. Epstein-Barr virus (EBV) DNA was detected in the patient's bone marrow and in a lymph node biopsy. Cells from the lymph node biopsy showed monoclonal rearrangements of immunoglobulin heavy chain genes but no rearrangements of T-cell receptor beta-chain genes or immunoglobulin kappa chain genes. Serological data indicated chronic active EBV infection. There was a slight increase of CD8 positive cells in peripheral blood and a normal response to T-cell mitogens. However, T-cell lines established with interleukin 2 from lymph node biopsy completely failed to kill autologous EBV-transformed B-cells and K 562 target cells. Moreover, in regression tests the patient's peripheral blood mononuclear cells completely failed to limit outgrowth of autologous EBV infected B-cells. We conclude that the patient's selective immuno-deficiency had led to the rapid development of EBV-associated monoclonal lymphoproliferation.

Antibodies, Viral↗
PubMed1989

Virus-specific and autoreactive T cell lines isolated from cerebrospinal fluid of a patient with chronic rubella panencephalitis.

Using a recently described technique for expanding of human T lymphocyte populations from cerebrospinal fluid (CSF), we investigated the local cellular immune response in a patient with chronic rubella panencephalitis. A total of 328 T cell lines (TCLs) was established by seeding CSF cells at limiting dilution into histoplates in the presence of irradiated feeder cells and phytohemagglutinin (PHA)-containing conditioned medium. 80% of TCLs expressed the CD4+CD8-, 5% the CD4-CD8+ phenotype and 15% of TCLs contained different proportions of CD4+ and CD8+ cells. Of 191 TCLs analyzed, 85 were cytotoxic, as shown by their lectin-dependent cytotoxicity against allogeneic uninfected target cells. Eight of them demonstrated specificity for the autologous, rubella virus-infected target cells. When tested for antigen-specific proliferative activity, 26 TCLs responded to rubella antigen, 16 TCLs reacted to myelin basic protein (MBP), four TCLs to proteolipid protein (PLP), four to galactocerebrosides and two to actin. Fourteen out of 16 MBP-specific TCLs also responded, to a minor degree, to rubella antigen and/or actin. The results showed that the persisting rubella infection had given rise to autoreactive T cells. Virus-induced autoreactivity to brain antigens may be an important pathogenetic mechanism in other chronic inflammatory disorders of the CNS.

Actins↗
PubMed1987

[Molecular biology aspects of neuroblastoma].

Neuroblastoma is one of the most frequent malignant tumors in childhood. Molecular and cytogenetic methods have led to important advances in our understanding of the biology of this tumor. Amplification and increased expression of the gene N-myc is correlated with the clinical stage. This may be a useful marker for monitoring tumor activity during therapy. In addition, karyotyping and flow cytometric DNA analysis may be useful diagnostic tools for staging and predicting the clinical outcome.

Child↗
PubMed1984

Partial C4 deficiency in subacute sclerosing panencephalitis.

In an immunogenetic study, 23 subacute sclerosing panencephalitis (SSPE) patients and their families were studied for the HLA region markers HLA-A, B, C, DR, BF, C2, C4A, C4B, GLO I, and PGM3. In addition, C3, C4, and factor B serum levels were determined. A highly significant association of C4A QO with SSPE was found. Furthermore, two rare haplotypes, C4A QOB QO, two C4ACh+ allotypes, and four Ch partial inhibitors were detected, which possibly impair the function of the C4 molecules. HLA-DR5 was increased. In addition, a number of rare HLA-A, C, B, DR haplotypes were observed. It is postulated that rare C4 molecular deficiency might be a predisposing factor in the pathogenesis of SSPE.

Complement C4↗
PubMed1984

Phenotypic markers and functional characteristics of T lymphocyte clones from cerebrospinal fluid in multiple sclerosis.

We have recently developed a technique for direct expansion of human T lymphocyte clones from cerebrospinal fluid (CSF) of patients with acute infections of the central nervous system (CNS). In the present study, T lymphocyte clones were established directly from the CSF of 4 patients with multiple sclerosis by limiting dilution in the presence of T cell growth factor and irradiated feeder cells. In 3 patients the CSF was obtained during an exacerbation of their disease. Cloning efficiencies ranged between 4 and 6%. About 40 clones per patient were available for surface marker analysis and functional studies. Typing of the clones for membrane antigens revealed the following results: 75-100% had the OKT4+8- and 0-25% the OKT4-8+ phenotype. Only one clone expressed both surface markers. When tested for PHA-dependent cytotoxicity, all OKT8+ clones and about 50% of the OKT4+ clones were found to express cytotoxic activity. Studies on the proliferative response showed that all OKT4+ and the majority of OKT8+ clones were capable of TCGF-independent, mitogen-induced proliferation. Screening of the clones for specific reactivity against a panel of antigens including measles virus, mumps virus, Epstein-Barr virus and myelin basic protein (MBP) did not reveal significant specific reactivity.

Adult↗
PubMed1984

[Sinus histiocytosis with massive lymphadenopathy--a virus-associated disease?].

Clinical course and laboratory data of three patients with sinus histiocytosis and massive lymphadenopathy ( SHML ) are described. In 80% of the cases a massive and painless bilateral enlargement of the cervical lymphnodes is the presenting feature; 25% show extranodal involvement. The etiology of SHML is as yet unknown. In two patients with a high rubella antibody titer we were able to demonstrate rubella antigen in the involved lymphnodes thus supporting an infectious etiology of SHML . A virus isolation was not possible, so that the definite proof of a viral infection of SHML could not be demonstrated. As a rule therapy is not necessary. The exceptions are outlined. The prognosis is good.

Adolescent↗
PubMed1983

Clonal expansion and functional analysis of virus-specific T lymphocytes from cerebrospinal fluid in measles encephalitis.

T cells were directly cloned from the cerebrospinal fluid (CSF) of a patient with acute measles encephalitis by limiting dilution in the presence of irradiated feeder cells and T cell growth factor (TCGF). A total of 42 colonies was established. Functional analysis revealed 27 of them to be derived from a cytotoxic T lymphocyte as demonstrated by the ability to exert phytohaemagglutinin (PHA)-dependent cytotoxicity against uninfected allogeneic PHA blasts. Twenty-three of the cytotoxic colonies were specific for measles virus and restricted to self HLA-A or -B antigens. Three clones were also found to give measles virus-specific proliferative responses. The results show that the CSF in measles encephalitis contains a highly enriched population of in vivo sensitized antigen-specific T cells. We propose that the clinical symptoms in measles encephalitis are caused by a T cell-mediated reaction against virus-infected brain cells.

Child↗
PubMed1983

Clonal analysis of HLA-restricted virus-specific cytotoxic T lymphocytes from cerebrospinal fluid in mumps meningitis.

T lymphocytes were cloned directly from the cerebrospinal fluid of a patient with mumps meningitis by limiting dilution in the presence of irradiated feeder cells and T cell growth factor. Of 84 colonies analyzed, 41 were cytotoxic, as shown by their ability to exert phytohemagglutinin-dependent killing. Of these, 39 showed specificity for the autologous mumps-virus infected target cells. The cytotoxic T cell colonies showed the same pattern of HLA restriction as bulk cultures of CSF lymphocytes. This study shows that it is possible to perform functional assays on inflammatory exudate cells at the clonal level. The data also suggest that recruitment of effector cells from the peripheral compartment into the meningeal spaces in mumps meningitis is highly antigen-specific.

Antibodies, Monoclonal↗