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H Knecht

Publications and source records attributed to H Knecht.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Epstein-Barr virus replication in Hodgkin disease].

Epstein-Barr virus (EBV) is present in up to 40% of Hodgkin's disease (HD). The viral genomes remain latent within Reed-Sternberg cells (RS cells), but the recent detection of Zebra protein in rare neoplastic cells of a few EBV+ HD cases, suggests an activation of EBV replication. We have studied fifty HD cases containing EBV genomes and expressing LMP1 protein (including five AIDS-related cases), by immunohistochemistry with anti-Zebra antibodies. Four of these cases (all HIV-) showed Zebra+ tumor cells. One of these four cases showed numerous Zebra+ neoplastic cells (approximately 1% of tumor cells) and positive staining for EA-R protein, thus indicating early gene expression. In situ hybridization with biotinylated BamHI W probe revealed in this case, a signal of unusual strength within some Reed-Sternberg cells, probably related to increased number of EBV genomes, thus suggesting EBV replication. Viral replication was finally confirmed in this case, by the detection of BLLF1 transcripts (encoding for the membrane antigen gp 350/220) using reverse transcriptase and polymerase chain reaction. Thus, a very few Zebra+ neoplastic cells are concerned by viral replication, most of them harboring EBV involved in an abortive, instead of a full lytic cycle. EBV replication in RS cells remains an exceptional event, but may provide clues to immunologic mechanisms of control of viral latency. Clinical implications need further investigations.

Adult↗
PubMed1993

Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin's disease and identical to those observed in nasopharyngeal carcinoma.

This study of 52 European patients with Hodgkin's disease (HD) expressing the latent membrane protein 1 (LMP1) oncogene within diagnostic Hodgkin and Reed-Sternberg (HRS) cells was performed to detect LMP1 isolates carrying deletions and to characterize them at a molecular and histologic level. Deletions were identified in 5 cases, clustered near the 3' end of the LMP1 gene, and histologically associated with numerous HRS cells. DNA sequencing showed homology with the deletions seen in the Asian nasopharyngeal carcinoma (NPC) isolates CAO and 1510. Our findings suggest that partial deletions of the LMP1 oncogene, associated with aggressive behavior in NPC CAO and NPC 1510, occur at a particular localization and confer a proliferative phenotype to lymphoid cells in HD.

Adult↗
PubMed1993

Demonstration of Epstein-Barr virus replication in Reed-Sternberg cells of Hodgkin's disease.

Epstein-Barr virus (EBV) is detectable in approximately 40% of cases of Hodgkin's disease (HD). The viral genomes remain latent but positive staining with anti-ZEBRA antibody in a small fraction of Reed-Sternberg (RS) cells of some cases of HD would suggest possible activation of EBV replication within these cells. We report the investigation of 40 cases of EBV-associated HD (including 5 human immunodeficiency virus [HIV]-positive cases) using anti-ZEBRA antibodies. Positive staining was found in only three (HIV-negative) cases. One of these three cases showed approximately 1% of ZEBRA-positive tumor cells, whereas the other two cases showed rare positive cells. In the case with 1% ZEBRA-positive cells, a strong signal was obtained with anti-EA-R antibody and BHLF1 oligoprobes, which indicated early gene expression. EBV replication could be shown in this case by nonisotopic in situ DNA-DNA hybridization, which showed markedly increased numbers of EBV genomes in a few RS cells. Viral replication was confirmed using reverse transcriptase and polymerase chain reaction that detected transcripts from the BLLF1 gene encoding for the membrane antigen gp350/220. EBV replication in RS cells seems to be an exceptional event but may provide clues to mechanisms of control of viral latency and assume clinical implications in the future.

Base Sequence↗
PubMed1993

[Childbirth without fear in case of Von Willebrand's disease].

We report two cases of von Willebrand (type I) disease with vWF antigen levels of 21 and 25%, vWF ristocetin cofactor concentrations of 32 and 30%, and coagulation FVIII levels of 10 and 50% respectively. Template bleeding times were 20 and 11 minutes respectively. Both of these women exhibited a progressive and marked improvement of the vWF/FVIII complex during pregnancy. In the first, all parameters had completely normalized in the 37th week when a cesarean section was performed without hemorrhagic complications. The second case had borderline normal levels of the vWF/FVIII complex in the 37th week and underwent normal delivery in the 39th week. The improvement persisted for at least one week post-partum and in the first case values were still higher 10th weeks after delivery than they had been prior to the pregnancy. These observations and similar cases in the recent literature suggest that obstetrical operations and normal delivery are not associated with major blood losses in cases of moderately severe vWD of type I. These patients probably will not need vWF/FVIII concentrates for adequate hemostasis.

Adult↗
PubMed1993

Expression of human recombination activating genes (RAG-1 and RAG-2) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T-type.

In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy (AILD) and in anaplastic large cell lymphoma of T-type (T-ALC), recombinase activating gene (RAG-1 and RAG-2) expression was assessed in six AILD and five T-ALC cases using a sensitive reverse transcriptase (RT) and competitive (C) polymerase chain reaction (PCR). RAG transcripts were not detectable in nine cases with high proliferating activity, suggesting that in most cases the proliferating cells are derived from mature (rearranged) lymphocytes. However, low levels of RAG transcripts were detected in one AILD and one T-ALC case and are consistent with either an involvement of immature lymphoid precursors in the proliferating pool or a deregulated T-cell maturation pathway with persistence of RAG expression. An association between RAG gene expression and poor response to therapy is possible but has to be tested in larger prospective series.

Animals↗
PubMed1993

Familial primary gastric lymphoma.

Familial lymphoma is uncommon and is usually associated with various forms of hereditary immunodeficiencies. Primary gastric lymphomas that occurred in three adults from the same family, who had no overt immunodeficiency or cancer of non-lymphomatous origin, are reported. Two sisters presented with a low grade lymphoma of the mucosa associated lymphoid tissue type. Their father presented with a high grade form of later onset. All lymphomas have been phenotypically characterised as being of B cell origin. Epstein-Bar virus DNA was detected by polymerase chain reaction in the biopsy specimen of the high grade lymphoma but bcl-2/JH protooncogene rearrangement, t (14:18), was not identified in either the low or high grade lymphoma specimens tested.

Aged↗
PubMed1993

Molecular analysis of the LMP (latent membrane protein) oncogene in Hodgkin's disease.

Molecular analysis of the LMP (latent membrane protein) oncogene was performed in 21 Epstein-Barr virus (EBV) positive cases of Hodgkin's disease (HD) with proven LMP gene expression. In each case, viral DNA of the LMP gene was assessed for polymorphism (deletions, insertions, mutations) by polymerase chain reaction (PCR) amplification with selected primers. Specificity of the amplified targets was proven by internal oligonucleotide hybridisation and nested primer PCR. Homogeneity of the 5' LMP gene region coding for the amino terminal, transmembrane, and short extracytoplasmic domains of the protein was identified in all cases. However, deletions or insertions of small DNA sequences within the coding region for the intracytoplasmic LMP domain were observed in about 20% of cases. In one of them, a 30-base-pair deletion was precisely localized by DNA sequencing. A particularly high frequency of DNA polymorphism (30% of cases) was found in the 3' untranslated LMP region. However, when analysing the LMP gene in seven benign conditions, no DNA polymorphism was found. These data suggest conservation of oncogenic LMP regions coding for the protein domains known to be associated with transforming capacities and immunogenic functions. They also show a considerable genomic heterogeneity of the coding region for the intracytoplasmic domain and the 3' untranslated mRNA region. This LMP DNA polymorphism identified within a localized (Swiss) population suffering from HD is unexpected. Its eventual clinical significance remains to be determined.

Antigens, Viral↗
PubMed1992

Expression of human recombination activating genes (RAG-1 and RAG-2) in Hodgkin's disease.

The differentiation status of Sternberg-Reed (SR) cells is still not well defined, primarily because of their scarcity in tumor biopsies of Hodgkin's disease (HD). In this study we have determined the genomic differentiation status of SR cells by quantitation of recombinase activating gene (RAG) expression. RAG genes are selectively transcribed in immature lymphoid cells. In B cells they are silent after genomic rearrangement has occurred, whereas in T cells they are downregulated during positive selection of double-positive thymocytes into single-positive cells. RNA from tumor biopsies either with numerous (11 cases) or a with few SR cells (16 cases) was assessed by a sensitive reverse transcriptase polymerase chain reaction (RT-PCR) and the results compared with established positive and negative controls. In all except two cases levels of RAG expression were within the range of those determined in negative controls. In both positive cases and in the positive control RAG mRNA was further quantitated by competitive PCR. In cases with abundant SR cells RAG expression was still below that observed in 10(-2) dilutions of positive controls. These results suggest that SR cells are derived from lymphoid cells, more differentiated than the pre-B or common thymocyte stage, which have already undergone genomic rearrangement. They show the value of assessing RAG expression by RT-PCR in the characterization of lymphoid malignancies.

Animals↗
PubMed1992

Epstein-Barr virus burden in Hodgkin's disease is related to latent membrane protein gene expression but not to active viral replication.

The Epstein-Barr virus (EBV) has been increasingly detected in Hodgkin's disease (HD), but its role in pathogenesis remains uncertain. We analyzed 20 specimens of HD known to contain EBV DNA by a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). The cases were assessed for the presence of RNA transcripts of the BNLF1 gene (coding for the viral latent membrane protein [LMP]) and the late replicative gene BLLF1 (coding for the principle envelope glycoprotein [gp220/350]). LMP RNA transcripts were found in 9 of 20 (45%) cases, mostly those containing many copies of viral DNA and of mixed cellularity (MC) histological subtype. Only one LMP RNA-positive case was also positive for RNA transcripts of the active replication gene BLLF1. Our results show that viral burden in HD is not primarily related to active viral replication, but is associated with LMP gene expression.

Adolescent↗
PubMed1992

[Hemophilia C, a deficiency of a contact phase protein which may involve a risk of hemorrhage].

Factor XI deficiency, also called hemophilia C, was first described in 1953. It is thought to constitute 7% of all disorders of the intrinsic pathway of blood coagulation. It represents the only deficiency of a contact phase protein associated with a bleeding tendency with widely variable expression. Eighteen members of 5 families with this deficiency have been investigated; only 3 exhibited a hemorrhagic diathesis: 2/4 homozygous (hemorrhages after surgical procedures and hematomas and after minor traumatism) and 1/10 heterozygous individuals (hematomas, epistaxis). All homozygotes had a prolongation of the PTT. The hemorrhagic tendency was higher among homozygous individuals (with very low factor XI activity), but 2 were asymptomatic. Heterozygotes may also bleed. This deficiency is found mainly in an Ashkenazy Jewish population. Our study shows that it occurs in an apparently autochthonous Swiss population. A detailed history and studies of other family members are necessary if there is suspicion of factor XI deficiency.

Adult↗
PubMed1992

Significance of the detection of Epstein-Barr virus DNA in lymph nodes in patients with Hodgkin's disease.

Epstein-Barr virus (EBV) DNA is frequently identified in benign and malignant lymphoproliferative conditions. As shown by in situ hybridization studies viral DNA is localized within malignant cells as well as benign lymphocytes. Clonal and nonclonal EBV genomes are present in Hodgkin's disease (HD), lymphomas of the immunocompromised host and reactive lymph node hyperplasia. Lytic infection with formation of linear genomes is observed in the same conditions but appears to be infrequent in HD as shown by quantitation of mRNA coding for viral capsid antigen. Expression of the oncogene LMP (latent membrane protein) is seen in Sternberg-Reed (SR) cells and immunoblasts of AIDS-related lymphoma and infectious mononucleosis (IM). In HD, the region of the BNLF1 oncogene coding for the amino terminal and transmembrane domains (associated with oncogenic function) of LMP appears to be homogeneous whereas the region coding for the intracytoplasmic (carboxy terminal) domain of LMP is heterogeneous. Cytological similarities between SR cells and immunoblasts of IM and AIDS-related lymphomas are consistent with the hypothesis that the BNLF1 oncogene is one possible inducer of morphological features of SR cells. Whether chromosomal integration of EBV DNA is an important factor in activation of such a transforming activity remains to be elucidated. EBV DNA positive and negative HD cases with numerous SR cells lack significant mRNA expression of the two recombinase activating genes (RAG-1 and RAG-2). Therefore the SR cells appear to be derived from lymphocytes beyond the pre-B-cell or common thymocyte stage which may or may not subsequently become infected by EBV.

Antigens, Viral↗
PubMed1992

[Demonstration of Epstein-Barr virus DNA and determination of immunoglobulin and T-cell receptor gene rearrangerments in diagnostic lymph node biopsies from patients with Hodgkin's disease].

Lymph node biopsies of 52 patients with Hodgkin's disease were analyzed by Southern blot hybridization for the presence of monoclonal rearrangements of immunoglobulin and T cell receptor genes. The same tissues were tested for Epstein-Barr virus DNA by the polymerase chain reaction using four different sets of primers. Monoclonal rearrangements were identified in only four tumors, whereas Epstein-Barr virus was present in 79% of biopsies. A correlation between the degree of infiltration by Reed-Sterberg cells, clonality and the presence of Epstein-Barr virus could not be found. These results are in agreement with similar studies reported in the literature. The nature of the malignant cell in Hodgkin's disease and the role of Epstein-Barr virus in the etiology of this tumor remains to be established.

Base Sequence↗
PubMed1991

[Persistent B-cell polyclonal lymphocytosis: a benign lymphoproliferative syndrome].

A further case of persistent polyclonal B-cell lymphocytosis is reported. This recently identified distinct clinicopathologic entity is frequently associated with the presence of the HLA-DR7 antigen. It follows a benign course and has so far been reported only in women smokers. The disorder is characterized by mild chronic peripheral lymphocytosis, the presence of characteristic binucleate lymphocytes on peripheral blood smears, and a polyclonal increase in serum IgM. In some cases, lymphadenopathies and/or splenomegaly are observed. Surface marker studies of peripheral lymphocytes demonstrate the polyclonal B-cell nature of this entity.

Adult↗
PubMed1991

Frequent detection of Epstein-Barr virus DNA by the polymerase chain reaction in lymph node biopsies from patients with Hodgkin's disease without genomic evidence of B- or T-cell clonality.

This study of 52 Swiss patients with Hodgkin's disease (HD), including 17 cases with a high content of Sternberg-Reed (SR) and Hodgkin (H) cells, was performed to determine the percentage of cases harboring Epstein-Barr virus (EBV) DNA and/or clonal rearrangements of Ig and T-cell antigen receptor (TcR) genes in diagnostic lymph node biopsies. Special attention was drawn to the heavily infiltrated cases to detect a possible relationship between clonality and EBV DNA identification. EBV DNA was detected by the polymerase chain reaction (PCR) using three different sets of specific primers. The viral origin of the amplification products was confirmed by hybridization with a radiolabeled internal probe or demonstration of a specific Sma I restriction site. Genomic rearrangement of Ig and TcR genes was studied by Southern blot analysis. EBV DNA was identified by PCR in 38 of 48 cases (79%). Clonal rearrangements were identified in only 4 of 52 cases (Ig genes) and were independent of the degree of infiltration by SR cells and the presence of EBV DNA. The absence of EBV DNA in three cases with numerous SR cells (only one of them showed clonal rearrangement) and the presence of only a few viral copies in four further cases with numerous SR cells (semiquantitative analysis of viral DNA by PCR was performed in 26 EBV-positive cases) suggests that this virus is modulating rather than an etiologic agent in a considerable proportion of HD cases.

B-Lymphocytes↗
PubMed1991

Different clinical presentations of a lupus anticoagulant in the same family.

A young man who had suffered several episodes of deep-vein thrombosis of the legs since the age of 20 had a myocardial infarction at the age of 33, at which time both a prolonged partial thromboplastin time (PTT), compatible with a lupus anticoagulant (LA), and decreased fibrinolytic capacity (FC) were found. His sister presented with deep-vein thrombosis of a leg and subsequent pulmonary embolism when she was 18 years old. She had a miscarriage three years later and developed a hemolytic-uremic syndrome at the age of 35. The PT and FC were normal. Laboratory investigations of the parents revealed positive antinuclear antibodies in the mother's serum but no anomaly in the father. This study suggests a familial tendency to develop autoimmune disorders associated with LA and thromboembolic complications related to decreased FC.

Adult↗
PubMed1991

Genotypic and phenotypic evidence of T-cell leukemia in a patient successfully treated by interferon-alpha for typical hairy cell leukemia.

A 53-year-old man was diagnosed to have typical hairy cell leukemia. Immunophenotyping of frozen splenic tissue showed clonality of hairy cells for mu lambda, confirmed by the corresponding immunoglobulin gene rearrangements. The patient was successfully treated with interferon-alpha (IF-alpha). In the fifth year of treatment with IF-alpha the morphology of peripheral blood mononuclear cells (PBMC) and of bone marrow infiltration changed with the appearance of numerous small to intermediate shaped lymphocytes of a T-helper phenotype. Frank leukemia, resistant to IF-alpha treatment and ultimately aggressive chemotherapy, developed. Emergence of this second clonal disease was confirmed by rearrangement studies performed on PBMC; rearrangements of both alleles of the TCR beta were identified, whereas the JH and lambda IVS genes were in germline configuration. The outgrowth of a second, malignant T-cell clone paralleled by the disappearance (down-regulation?) of the initial B-cell clone while under cytokine treatment is consistent with the possibility that IF-alpha favoured the emergence of this second clone.

Bone Marrow↗