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H Stein

Publications and source records attributed to H Stein.

At least 271 records · Page 15Linked to original sources
PubMed1995

Frequent presence of latent Epstein-Barr virus infection in peripheral T cell lymphomas. A review.

Two-hundred and four cases of peripheral T cell lymphoma (PTCL) occurring in Europeans without any sign of HIV-infection were investigated for their association with an Epstein-Barr virus (EBV) infection. Polymerase chain reaction (PCR) was applied for EBV-DNA detection, in situ hybridisation (ISH) for the cellular localization of EBV-encoded small nuclear RNA (EBER) and immediate early gene expression (BHLF) and immunohistology (IH) for the detection of EBV-encoded latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER-ISH produced congruent results in almost all cases with amplifiable DNA, leading to the finding of an overall frequency of EBV presence in 87/204 (42.6%) of the PTCL cases. Through EBER-ISH, the virus was identified to be exclusively present in small and blastic bystander lymphocytes in 29 cases, whilst an additional infection of neoplastic T cells was observed in the remaining 58 EBV-positive cases. The entity presenting with the most frequent EBV infection of tumour cells was that of angioimmunoblastic type PTCL, whilst the primary cutaneous PTCLs only seldom harbored the virus. Forty-eight of the EBV-positive TCLs showed an infection of a small proportion (1-20%) of the tumour cell population, whilst another ten cases, belonging to the pleomorphic TCL (PMTCL) group, displayed an infection of several to almost all neoplastic T cells (20-100%). Additional lytic EBV-infected cells could be detected in four cases by BHLF-ISH. LMP1 expression was present in a small proportion of the neoplastic T cells in 24 of the 58 cases with tumour cell infection, whilst an EBNA2 expression was detectable only in one case. Some non-malignant EBV-infected B-immunoblasts and Hodgkin/Reed Sternberg-like cells also expressed LMP1 in several cases. Our data imply a role of EBV in the pathogenesis of only a few PMTCL cases with predominant tumour cell infection, whilst the pathogenic significance of an EBV infection in the other PTCLs remains unclear due to the usually partial infection of the neoplastic cell component.

Antibodies, Monoclonal↗
PubMed1995

Anaplastic large cell lymphoma: update of findings.

The problem of anaplastic large cell lymphoma (ALCL) is extensively reviewed by depicting the clinical, pathological and biological characteristics of the four main varieties of ALCL: common, Hodgkin's like/Hodgkin-related, lympho-histiocytic, and giant-cell rich. Special emphasis is given to the differential diagnosis between ALCL Hodgkin like and Hodgkin's disease in the light of possible therapeutical differences.

Genotype↗
PubMed1995

Antiproliferative effect of human interleukin-4 in human cancer cell lines: studies on the mechanism.

Interleukin-4 (IL-4) plays an important role in activating the immune system against malignant cells. The human interleukin-4 receptor (hIL-4R) is not only expressed by hematopoietic cells but also on a large number of tissue specimens which include colon, breast and lung carcinomas. In this study we report that rhIL-4 has an antiproliferative effect on 2 out of 3 non-small cell lung carcinoma (NSCLC) cell lines in vitro as measured by human tumor cloning assays (HTCA). In comparison, rhIL-4 had no effect on the growth of small cell lung carcinoma cell lines (SCLC) in vitro. The response towards the cytokine is correlated with expression of at least 1500 high affinity receptors/cell for hIL-4 on the responsive cell lines. Xenotransplanting the human lung tumor cell lines into nude mice followed by 12 days of systemic treatment of the mice with rhIL-4 revealed a significant growth retardation of the IL-4R positive NSCLC cell lines when compared with the controls, whereas the growth of the IL-4R negative SCLC cell lines was unaffected also in vivo. Studies of possible mechanisms involved in the antiproliferative effect of rhIL-4 showed that rhIL-4 does not induce apoptosis or modulation of the transcription factor c myc in the responsive NSCLC cell lines. Additionally, the expression of the epidermal growth factor receptor (EGFR), which is discussed as mediating autocrine/paracrine growth stimulation of NSCLC, is unaffected by rhIL-4. However, we have observed that rhIL-4 inhibited G1-S-phase cell cycle progression. We conclude that rhIL-4 has an antiproliferative effect on the growth of some NSCLC in vitro and in vivo. The mechanisms involved remain to be further elucidated.

Animals↗
PubMed1995

Burkitt's lymphomas express VH genes with a moderate number of antigen-selected somatic mutations.

The normal counterpart of the neoplastic B cells occurring in Burkitt's lymphomas (BL) is an issue of controversial debate. To clarify this matter, a semi-nested primer polymerase chain reaction was performed to amplify the VDJ rearrangements of the immunoglobulin heavy chain (VH) gene of DNA extracts from 10 (8 sporadic and 2 endemic) BL cases. The resulting amplificates were sequenced for comparison with known germ line VH segments. The control cases comprised six cases of B cell chronic lymphocytic leukemia and six cases of mantle cell lymphoma known to display naive nonmutated, ie, pre-germinal center VH configurations; and eight cases of follicular center lymphoma known to display mutated VH genes with signs of a still-ongoing mutation reaction, characteristic for germinal center cells and lymphomas that derive therefrom. The results of this approach revealed that both sporadic and endemic BL express mutated VH genes with a mutation frequency considerably lower (4.9% and 5.4%, respectively) than that observed in follicular center lymphoma (11.8%). In addition, after subcloning the amplificates, sequence analysis revealed no signs of ongoing mutations. These results led us to conclude that the derivation of neoplastic B cells in BL is definitely not from naive, nonmutated pre-germinal center B cells. Instead, our findings support the view that BL cells stem either from early centroblasts that are arrested after an initial hypermutation reaction, or from germinal center B cells that have differentiated in terms of surface immunoglobulin profile and mutation pattern but not in terms of morphology and proliferation toward SIgM+ IgD- memory B cells because of the deregulated c-myc gene expression.

Burkitt Lymphoma↗
PubMed1995

Quantitative analysis of chondroitin sulphate retention by tannic acid during preparation of specimens for electron microscopy.

The ability of tannic acid to enhance binding of glycosaminoglycans to purified collagen was analysed in an in vitro system using amino sugar analysis on an amino acid analyser, transmission electron microscopy, and scanning electron microscopy. Collagen was purified by digestion with trypsin, papain, and hyaluronidase. Purified collagen was incubated with hyaluronic acid or with chondroitin sulphate glycosaminoglycan and then treated with tannic acid. Tannic acid was found to enhance retention during preparation for electron microscopy of either of the glycosaminoglycans onto collagen fibres. The ability of tannic acid to enhance binding of collagen and glycosaminoglycans might explain, at least in part, its structural reinforcement effect on resected synovial joint-apposing surfaces during preparation for scanning electron microscopy.

Amino Sugars↗
PubMed1995

Frequent expression of IL-7 gene transcripts in tumor cells of classical Hodgkin's disease.

Interleukin-7 (IL-7) is a pleiotropic cytokine acting mainly on cells of the hematolymphoid system. In vitro studies have shown enhanced proliferation of acute lymphoblastic leukemia cells in response to IL-7. On the other hand, tumor cell lines transfected with a functioning IL-7 gene and subsequently transplanted into mice resulted in a prominent inflammatory infiltrate and reduced tumorigeneicity. These data suggest an important role of this cytokine in the pathophysiology of lymphoid neoplasms. Because little is known about the in vivo expression of this cytokine in various neoplastic and nonneoplastic lesions of the lymphoid system, we examined frozen and paraffin-embedded tissue samples of normal, reactive, and malignant lymphoid lesions using in situ hybridization with a 35S-labeled RNA probe specific for IL-7. Tumor cells of nodular sclerosing and mixed cellularity type of Hodgkin's disease displayed IL-7-specific signals in 24 of 31 cases. Among reactive lesions, only thymic tissue showed labeling within both cortex and medulla (4 of 7 cases), whereas in tonsils clear-cut IL-7-specific signals could not be found. Tissues infiltrated by B-type chronic lymphocytic leukemia or T- or B-type lymphoblastic lymphoma showed cytokine-specific signals in only one case of lymphoblastic lymphoma in rare reactive cells. In conjunction with the finding of elevated levels of IL-7 in the serum of many patients with Hodgkin's disease, our data suggest an important role of this cytokine in the pathogenesis of Hodgkin's disease. The prominent reactive infiltrate observed in most cases of Hodgkin's disease could be a consequence of elevated local levels of this cytokine as similar infiltrates are also observed in tumors in mice resulting from injection of tumor cell lines transfected with a functioning IL-7 gene.

Child↗
PubMed1995

CD30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule.

The expression, serological detection, and possible functional role of the CD30 antigen in Hodgkin's disease and anaplastic large cell lymphoma is well documented. In embryonal carcinoma (EC), the expression of this cytokine receptor has been demonstrated only by immunohistology. Because the CD30 monoclonal antibody Ki-1 was found to cross-react with an unrelated molecule, we examined by in situ hybridization testicular germ cell neoplasms for the presence of CD30-specific transcripts. CD30 mRNA was detectable in the tumor cells of 9 of 9 cases of EC or mixed germ cell tumors with an EC component but in no other nonlymphoid tumors. Thus, the CD30 transcript expression pattern proved to be identical to the immunostaining pattern seen with the CD30-specific monoclonal antibody Ber-H2. By Northern blot analysis, CD30 transcripts could be demonstrated in the EC cell line Tera-2. Employing a highly sensitive second generation sandwich enzyme-linked immunosorbent assay, we could detect the soluble CD30 molecule in 8 of 8 sera from patients with a diagnosis of EC but not in 8 of 10 sera from patients with other testicular germ cell tumors. In fetal tissue, no CD30-expressing germ cells or epithelial cells could be observed. Thus, the cellularly expressed CD30 marker for testicular neoplasms of EC type. Moreover, the serum levels of soluble CD30 antigen seem to be a promising parameter for monitoring patients with EC.

Adolescent↗
PubMed1994

Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types.

The expression of mucin MUC2 was investigated in normal colonic tissue, in colonic adenomas and in carcinomas of the mucinous and non-mucinous type. The latter were subdivided into carcinomas originating from the adenoma-carcinoma sequence (ACS) and de novo (DN) carcinomas. The expression was assayed by immunohistochemistry with the monoclonal anti-MUC2 antibody CCP58 and by mRNA semiquantitation. MUC2 protein epitope CCP58 was strongly expressed in 21% of normal colonic tissues, in 40% of villous and in 48% of tubular adenomas. Mucinous carcinomas exhibited strong expression in 72%, ACS carcinomas in 21% and DN adenocarcinomas in none of the tumors investigated. Compared with the adjacent non-malignant tissue (transitional mucosa), CCP58 epitope expression in the tumor was higher in 74% of mucinous carcinomas, but equal or lower in 69% of ACS carcinomas and in 100% of de novo carcinomas. The alterations of MUC2 expression detected by immunohistochemistry in adenocarcinomas were confirmed on mRNA level. These data indicate that the MUC2 expression pattern is different in the 3 carcinoma types investigated. MUC2 over-expression occurs in the adenomatous tissue. It is always maintained in mucinous carcinomas, but frequently decreased in non-mucinous ACS carcinomas. DN carcinomas are most frequently associated with decreased expression of MUC2.

Adenocarcinoma, Mucinous↗
PubMed1994

Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement and somatic mutations in the VH genes.

The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question. Immunophenotypic studies favor a relation to the lymphoid lineage with the existence of B- and T-cell types. However, studies on the detection of antigen (Ag) receptor gene rearrangements provided inconsistent results. They concur in that rearranged Ig and T-cell receptor (TCR) genes are not demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this is because of the insensitivity of the method of detection or a real absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain reaction (PCR) method with high sensitivity was applied, allowing the detection of less than 50 cells with clonally rearranged IgH genes in a mixture of 100,000 germline or individually rearranged cells. In 67 cases of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes, the VH segment of six contained considerable somatic mutations. These results suggest that the demonstrated VDJ rearrangements stem from the HRS cells themselves and that the HRS cells of cases with rearranged IgH genes are B-cell related and correspond in their differentiation stage either to naive pregerminal center B cells or (more commonly) to germinal center/postgerminal center-derived memory B cells.

Amino Acid Sequence↗
PubMed1994

Mantle cell (previously centrocytic) lymphomas express VH genes with no or very little somatic mutations like the physiologic cells of the follicle mantle.

To clarify whether mantle cell lymphomas (MCLs) are related to naive pre-germinal center B cells (expressing nonmutated rearranged VH genes) or to germinal center-derived memory B cells (expressing mutated rearranged VH genes), clonal IgH gene rearrangements using DNA from six MCLs were polymerase chain reaction (PCR)-amplified and analyzed for the presence of somatic mutations. For comparison, six cases of B-chronic lymphocytic leukemia (B-CLL) known to display nonmutated rearranged VH genes and six cases of follicle center lymphomas (FCLs) known to display mutated rearranged VH genes were included in our study. The VH region sequences of the six MCLs showed, like those of the six B-CLL cases, no or very little somatic mutations, in contrast to the VH sequences of the six FCL cases, all of which were highly mutated. This is indicative of MCL, like B-CLL, being derived from naive pre-germinal center B cells and furthermore underscores the postulated relationship of MCLs with the B cells of the normal follicular mantle zone because it has recently been shown that this mantle zone is solely or at least largely composed of naive (nonmutated) B cells.

Gene Rearrangement↗
PubMed1994

Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas.

The (2;5)(p23;q35) translocation which results in the fusion of the NPM (nucleophosmin) gene on chromosome 5q35 with the novel ALK (anaplastic lymphoma kinase) gene on chromosome 2p23 [S.W. Morris et al., Science (Washington DC), 263: 1281-1284, 1994] is associated with Ki-1 (CD30)-positive anaplastic large cell lymphomas (ALCL); a group of morphologically and immunophenotypically heterogenous high grade large cell lymphomas (LCL), which share many characteristics with Hodgkin's disease (HD), including the presence of variable numbers of Reed-Sternberg-like cells and the expression of CD30 antigen. Using a DNA probe immediately 5' to the NPM coding sequences, we have examined NPM gene rearrangements by Southern blotting in 5 Ki-1-positive lymphoma cell lines carrying a translocation involving the 5q35 breakpoint and in 25 Ki-positive lymphoma tumors, including 9 HD. Using this method, we detected rearrangements in all cell lines with apparent clustering of the breakpoints. Analysis of 25 Ki-1-positive lymphomas indicated that only 4 neoplasms, including two HD, had NPM gene rearrangements. Thus, our findings suggest that only a subset of ALCL has detectable involvement of the NPM gene. In addition, the presence of NPM gene rearrangements in HD indicates the involvement of this gene in a fraction of HD. Thus, NPM gene rearrangements may identify a certain subtype in ALCL and HD which may be closely related.

Chromosomes, Human, Pair 2↗
PubMed1994

Low-grade non-Hodgkin's lymphoma after high-grade non-Hodgkin's lymphoma in a child with ataxia telangiectasia.

BACKGROUND: Non-Hodgkin lymphomas (NHL) account for approximately 50% of neoplasms in patients with ataxia telangiectasia (AT). Prognosis is poor. Published data regarding the treatment of NHL in patients with AT suggested that these children respond poorly to therapy. The authors report on an infant with AT with mediastinal high-grade T-NHL who remained in continuous complete remission after chemotherapy. Diagnosis of AT was established after tumor diagnosis. METHODS AND RESULTS: The 7-month-old boy was treated according to the acute lymphoblastic leukemia-Berlin, Frankfurt, Münster 86 protocol. The therapeutic response was prompt, but therapy had to be stopped because of severe side effects. Surprisingly, the boy remained in a stable complete remission for 3 1/2 years. Then tumors in both kidneys occurred and the child died a few months later. Postmortem examination demonstrated large tumors in both kidneys caused by a low-grade malignant lymphoma of B-cell lineage. CONCLUSION: Congenital immune deficiency should be ruled out at diagnosis of rare malignancies in respect to age. NHL in patients with AT can be cured, but poor tolerance to chemotherapy has to be considered. Patients whose disease has been cured may be at high risk for development of a second independent malignancy.

Ataxia Telangiectasia↗
PubMed1994

Patterns of cytokine gene expression in infectious mononucleosis.

Primary infection with Epstein-Barr virus (EBV) may arise as infectious mononucleosis (IM) in adolescents and young adults. Morphologically, IM-affected lymphoid tissue is characterized by expanded interfollicular areas with formation of atypical lymphoid blasts. It is assumed that morphology and clinical presentation of IM are related to characteristic patterns of cytokine production by EBV-infected and reactive cells. We studied IM tonsils of eight patients and six normal tonsils with a double in situ hybridization procedure using [35S]-labeled RNA probes specific for various cytokines and digoxigenin-labeled probes for the detection of the nuclear EBV encoded RNA transcripts, EBER 1 and 2. All of the IM cases displayed the same distinct cytokine gene expression pattern. When compared with interfollicular areas of normal tonsils, expression of lymphotoxin (LT), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, but not IL-8 or IL-1 alpha was strongly enhanced in interfollicular areas in IM tonsils. LT was expressed predominantly by EBV-infected cells. TNF-alpha transcripts were also present in EBV-infected cells, although in smaller proportions. IL-6 specific signals were only found in few EBV-infected cells. IL-1 alpha-, IL-1 beta-, and IL-8-specific signals were not observed in EBV-infected cells, but were present at high signal intensity in many cells within and around foci of EBV-infected cells (IL-1 beta), next to areas of necrosis (IL-8, IL-1 beta), or in epithelial cells (IL-1 alpha). These data suggest that EBV infection in form of IM results in induction of specific sets of cytokine genes in EBV-infected and in neighboring EBV-negative cells contributing to the characteristic morphology and cellular arrangement of the lesion as well as the clinical presentation.

Cytokines↗
PubMed1994

The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen.

Tissue distribution and expression on mitogen and virally stimulated lymphocytes render the ACT35 molecule a human lymphocyte activation antigen which as yet could not be clustered. Expression cloning of the ACT35 antigen from a pCDM8 library of the HUT-102 cell line revealed strong homology of the cDNA and its encoded protein sequence with the formerly described rat OX40 antigen. The 1.4-kb nucleotide sequence and the deduced 277-amino acid sequence of the single transmembrane protein were 65% and 63% identical, in human and in rat, respectively. Conservation included one N-linked glycosylation site and one protein kinase C phosphorylation site. When expressed in COS-1 cells, the cDNA presented properties comparable to the native ACT35 antigen and the rat OX40 molecule (relative molecular mass 48,000). Thus, the ACT35 protein corresponds to the hitherto unknown human OX40 antigen and is, therefore, another member of the tumor necrosis factor/nerve growth factor receptor (TNFR/NGFR) family. After applying fluorescence in situ hybridization, the human ACT35/OX40 gene could be mapped to chromosome band 1p36 and is, thus, linked to the genes for TNFR II and CD30.

Amino Acid Sequence↗
PubMed1994

Gallstone shrapnel contamination during laparoscopic cholecystectomy.

The fate of lost gallstones in the peritoneal cavity following laparoscopic cholecystectomy is unknown. We report a case of microabscesses and granuloma formation in the peritoneal cavity and abdominal wall caused by infected gallstone shrapnel due to rupture of the gallbladder during extraction.

Abdominal Abscess↗