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Biomedical subjects

F Berger

Publications and source records attributed to F Berger.

At least 235 records · Page 13Linked to original sources
PubMed1995

Detection of EBV mRNA in nodular sclerosis type of Hodgkin's disease using in situ hybridization with EBER 1 and EBER 2 probes with regard to the immunophenotype of Reed-Sternberg cells.

Hodgkin's disease (HD) is a heterogenous disorder in terms of morphology, immunophenotype, genotype and association with viruses. Seroepidemiologic, immunohistochemical and molecular studies suggest that Epstein-Barr Virus (EBV) plays an important role in the pathogenesis of HD. We used in situ hybridization (ISH) with digoxigenin-labeled EBER 1 and EBER2 probes to examine a series of 28 lymph node specimens from untreated patients from Poland with the nodular sclerosis NS 1 and NS 2 subtypes of HD to detect EBV mRNA in Reed-Sternberg cells (RSC), or in small non-neoplastic lymphocytes called "bystander cell" (ByC). EBV mRNA was detected in 12 of 28 cases (32.1%). Furthermore, the expression of Latent Membrane Protein (LMP) of EBV strongly correlated with expression of EBER 1 and EBER 2 in RSC but not in "bystander cells", which were LMP negative. The correlation between EBV status and immunophenotype of RSC are discussed.

Herpesvirus 4, Human↗
PubMed1995

The expression of Epstein-Barr virus latent proteins is related to the pathological features of post-transplant lymphoproliferative disorders.

Transplant recipients are at increased risk for the development of post-transplant lymphoproliferative disorders (PTLDs). PTLDs harbor genomes of the Epstein-Barr virus, a herpesvirus that immortalizes B cells in vitro. At least five viral proteins are required for immortalization. Two of them are particularly important. Latent membrane protein (LMP) has transforming activity in fibroblasts, and Epstein-Barr antigen (EBNA)2 transactivates the expression of numerous cellular and viral genes. To determine whether the expression of EBNA2 and LMP is related to the histological and clinical presentation of PTLD, we tested their expression in 14 Epstein-Barr virus-positive cases. Using monoclonal antibodies to EBNA2 and LMP on paraffin sections, we found an expression of both proteins in 2 of 3 polymorphic PTLD and in 7 of 8 cases of monomorphic, large cell PTLD, without plasmacytic differentiation. One polymorphic and one large cell PTLD expressed LMP only. LMP and EBNA2 were found particularly in immunoblasts. The number of positive cells was extremely variable in the different cases as well as within the same biopsy. Three cases of PTLD had morphological and phenotypical features of plasmacytomas and did not stain for EBNA2 or LMP. This suggests that the expression of EBNA2 and LMP is related to the differentiation stage of the infected cells and that other viral or cellular proteins may contribute to tumor growth.

Antigens, Viral↗
PubMed1995

[Mid-term failure of balloon dilatation treatment of antral stenosis induced by caustics].

We report the case of an antral stricture following lye ingestion. The patient was treated by 3 dilations using a through-the-scope balloon dilator, initially with good results. One year later, the recurrence of the symptoms led to 2 other sessions of dilation without success and a partial gastrectomy was performed. The intensity of the gastric wall fibrosis on the surgical specimen, probably responsible for major motor impairment, accounts for the discordance between the good endoscopic result and the clinical failure. Endoscopic dilation of lye-induced gastric strictures could be a temporary alternative to surgical resection because the gastric wall fibrosis blemishes the long-term functional result.

Burns, Chemical↗
PubMed1995

Mucosa-associated lymphoid tissue lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct subgroup of non-Hodgkin's lymphoma with a particular clinicopathologic behavior. The gastrointestinal tract is involved in two thirds of the cases, but it may be observed in lung, breast, bladder, conjunctiva, kidney, liver, skin, salivary glands, thyroid, and thymus. This type of lymphoma tends to appear in patients with a history of autoimmune disease or chronic inflammatory disorders. In the stomach, this lesion is induced by Helicobacter pylori and is characterized by an accumulation of lymphoid tissue leading to chronic gastritis. The preceding lymphoid disorder is represented by Sjögren's syndrome, Hashimoto thyroiditis, and interstitial lymphoid pneumonia in the thyroid, salivary glands, or lung, respectively. Lymphoma cells initially arise from the marginal zone localized around reactive follicles and secondarily invade epithelial tissue to form the characteristic lymphoepithelial lesion. Patients with gastrointestinal MALT lymphoma generally present with localized disease without any adverse prognostic factors. These patients have long survival rates. Recurrences may appear in the same organ or in other extranodal sites. Nongastrointestinal MALT lymphoma patients seem to have a similar outcome. Patients may be treated with surgery or radiotherapy if the disease is localized, or with single-agent chemotherapy if it is disseminated. Reversion of the chronic inflammatory disorder with antibiotics, such as for gastric involvement, is a new observation that may change therapeutic options in the future.

Breast Neoplasms↗
PubMed1994

p53 genetic abnormalities and myc activation in human lung carcinoma.

p53 mutations and myc gene amplification and expression were studied in 119 lung carcinomas of all histological types. A mutant p53 immunophenotype was previously found in 47% of these tumors by immunohistochemical analysis. Seven cases exhibited p53 genomic rearrangements on Southern blots. Elevated levels of p53 transcript were found in 12 carcinomas (10%) and decreased levels in 27 carcinomas (23%) on Northern blots. In most of the cases, low levels of transcript were associated with negative immunostaining, whereas elevated levels of mRNA were related to positive immunostaining (mutant immunophenotype). p53 RT/PCR analysis in 10 tumors with absence of transcript on Northern blots revealed only weak or absent expression of normal and/or altered size transcripts. These abnormal transcripts showed deletions, insertions or splicing abnormalities. Taken together, p53 abnormalities were found in 66% of lung carcinomas [52% of neuroendocrine (NE) carcinomas and 75% of NSCLC]. c-myc was found to be activated in 24% (10/42) of these NE and in 48% (33/69) of these NSCLC carcinomas using Southern- and Northern-blot techniques. In addition, L- and N-myc genes were also activated in 26% (10/42) of NE carcinomas. No correlation was found between p53 mutations and myc activation in SCLC or in NSCLC, but their association was significantly more frequent in NSCLC than in SCLC. These results indicate that the p53-positive immunophenotype uncovers the occurrence of p53 point mutations in lung cancer and that p53 and c-myc gene alterations are important but represent independent occurrences in the development of lung tumors.

Base Sequence↗
PubMed1994

Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias.

Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B-lymphoid tumors (particularly mantle-cell lymphoma [MCL]). Its deregulation is thought to perturb the G1-S transition of the cell cycle and thereby to contribute to tumor development. As suggested by previously published studies, rearrangement of the 3' untranslated region (3' UTR) of CCND1 may contribute to its activation in some lymphoid tumors. To define further the prevalence of such rearrangements, we report here the result of the molecular study of 34 MCL and six t(11q13)-associated leukemias using a set of probes specific to the different parts of the CCND1 transcript. We also sequenced the entire cDNA of the overexpressed CCND1 transcripts in a t(11q13)-associated leukemia. DNA from four of these 40 patients showed rearrangement of the 3' UTR of CCND1 coexisting with major translocation cluster (MTC) rearrangement. Southern blot and sequence analyses showed that, as a result of these rearrangements, the 3' AU-rich region containing sequences involved in mRNA stability and in translational control is eliminated. Moreover, the finding that the CCND1 mRNA half-life was greater than 3 hours (normal tissues, 0.5 hours) in three t(11q13)-associated cell lines stresses the importance of posttranscriptional derangement in the activation of CCND1. Finally, we did not observe any mutation in the coding frame of the CCND1 cDNA analyzed.

Amino Acid Sequence↗
PubMed1994

Nonfollicular small B-cell lymphomas: a heterogeneous group of patients with distinct clinical features and outcome.

Two hundred sixteen patients with a nonfollicular small cell lymphoma followed up in our department over a 5-year period have been reviewed to define the clinical behavior and survival of patients with each histologic subtype. The respective frequencies of major subtypes were: small lymphocytic/lymphoplasmacytoid lymphoma (immunocytoma, SL/LPL), 28%; large cell-rich immunocytoma (LCRI), 7%; mantle cell lymphoma (MCL), 24%; mucosa-associated lymphoid tissue-lymphoma (MALT-L), 20%; other rare subtypes, 6%; and nonclassified or nonreviewed, 14%. The SL/LPL patients and the MALT-L patients had a relatively indolent disease, usually disseminated for SL/LPL and usually localized for MALT-L. Both subtypes have a long time to treatment failure (TTF; median, 48 and 58 months, respectively) and long survival (median, 118 and 98 months, respectively). The LCRI patients or the MCL patients had more aggressive clinical or biologic features and experienced shorter TTF (median, 26 and 14 months, respectively) and shorter survival (median, 55 and 52 months, respectively). None of these histologic subtypes was associated with a significant cure rate. MALT-L patients did relapse regardless of the initial localization or treatment and at a similar rate to the SL/LPL patients. Factors associated with a worse outcome in nonfollicular small cell lymphoma patients are identical to those described in other lymphoma subtypes: advanced clinical stage, poor performance status, high tumor bulk, and high lactic dehydrogenase or beta 2microglobulin levels. For patients with disseminated disease, standard chemotherapy regimens did not allow a long TTF; therefore, new therapeutic strategies must be developed.

Adult↗
PubMed1994

Expression and tumorigenicity of the Epstein-Barr virus BARF1 gene in human Louckes B-lymphocyte cell line.

We previously showed that the Epstein-Barr virus, which encodes the BARF1 gene, could transform rodent fibroblasts. In this work, the expression of the BARF1 gene was studied in the human Louckes B-lymphocyte cell line. Introduction of the BARF1 open reading frame under the control of the Mo-MuLV LTR promotor into nontumorigenic Louckes lymphoid cells led to the activation of the c-myc protooncogene and increased expression of the B-cell surface proteins, the transferrin receptor, CD21, and CD23. BARF1-expressing cells induced a diffuse lymphoma-like tumor in newborn rats treated with anti-thymocyte serum that was, however, transient and regressed after 3-4 weeks as the immune system recovered. The tumor induction was similar to that observed with lymphoid cell lines in vitro generated by infection with the B95-8 virus strain, in which lytic antigens are expressed at low levels. After long-term culture, Louckes cell clones lost expression of the BARF1 gene and were unable to induce tumors.

Antigens, CD↗
PubMed1994

Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas.

The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin G1 gene family, and thereby to contribute to tumorigenesis. We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC). We have determined the nucleotide sequence for a portion of the MTC region, and constructed chromosome 11-specific oligonucleotides that were in conjunction with a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to PCR detection. The sizes of the amplified bands, the existence or not of a Sac I site in the PCR products, and nucleotide sequencing of the amplified DNA from four patients showed that the breakpoints share a remarkable tendency to tightly cluster within 300 bp on chromosome 11, some of them occurring at the same nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH. Our findings indicate that a BCL1 rearrangement can be detected using this approach in roughly one half of the MCL patients. This has implications for both the diagnosis and the clinical management of MCL.

Base Sequence↗
PubMed1994

Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine therapy of brain tumors?

The secosteroid 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) is the major biologically active metabolite of vitamin D. Antitumor activity of this hormone has been observed on several cell lines and on breast cancer in vivo. The purpose of this in vitro study was to determine the possible effect of 1,25(OH)2D3 on glioma cells. Two glioma cell lines from rat (C6) or human (GHD) origin were cultured in the presence of 1,25(OH)2D3. The sensitivity of these cells to 1,25 (OH)2D3 was assessed with a colorimetric MTT assay. A cytotoxic effect of 1,25(OH)2D3 was detected at concentrations around 10(-8) M. A lag period of 3 days was required between the onset of the treatment and the observation of the effects. However, the continuous presence of 1,25(OH)2D3 is not required since cell death occurred even when C6 cells were challenged for 24 hr with 1,25(OH)2D3 and then cultured in the absence of the hormone. In addition, 1,25(OH)2D3 regulates the expression of its own receptors in C6 glioma. These results provide to our knowledge the first evidence for a cytotoxic effect of 1,25(OH)2D3 on rat and human glioma cells and could offer both an experimental model to study a programmed cell death in a brain-derived cell line and a new strategy for the inhibition of glioma growth in vivo.

Animals↗
PubMed1994

Altered homologous and heterologous gap-junctional intercellular communication in primary human liver tumors associated with aberrant protein localization but not gene mutation of connexin 32.

Gap-junctional intercellular communication (GJIC) in 20 primary human liver tumors with different degrees of malignancy has been studied at the functional and molecular levels. When GJIC capacity was determined by dye-transfer assay performed directly with freshly removed tumor tissue, significant reduction was found in all samples, regardless of their morphology. In addition, a selective lack of GJIC between tumor and surrounding non-tumorous cells was observed in some cases, probably due to the physical separation between them resulting from encapsulation of tumors. There was, however, no essential change in the level of expression of the major liver gap-junction protein, connexin (cx) 32, in liver tumors as measured by Northern and Western blot analyses. Immunohistochemical study revealed aberrant localization of cx 32 in the majority of malignant liver tumors. Instead of cytoplasmic membrane localization at intercellular contacts, cx 32 was detected mainly either intracytoplasmically or in plasma membrane free from contact with other cells. We did not detect any mutation in the coding sequence of the cx 32 gene from any of the human liver tumors we tested. Thus it is likely that the aberrant localization of cx 32 in tumor cells is due to disruption of the mechanisms for establishment of this protein into gap-junction plaques, rather than to structural abnormality of the cx 32 protein itself. Another member of the connexin family, cx 43, not detectable in non-tumorigenic hepatocytes, was expressed in several tumors, especially in invasive areas, but was detected in only a few tumor cells and was localized intracytoplasmically, suggesting that cx 43 protein is not involved in GJIC in the tumors.

Adult↗
PubMed1994

Chemolabeling of frozen cerebral tissue proteins and immunopurified products with biotin and digoxigenin: physicochemical characteristics of biotinylated and digoxigeninated products.

Biotinylation and digoxigenination have been compared for labeling proteins from a total frozen tissue extract and from products of immunopurification with anti-RAR beta (retinoic acid receptor beta). The detection of biotinylated and digoxigeninated proteins was found to be easier and more sensitive than detection of silver-stained proteins after two-dimensional electrophoresis. Although biotinylated or digoxigeninated proteins can be detected with avidin conjugates or anti-digoxigenin antibodies, they can also be detected with specific antibodies such as anti-RAR beta antibodies. Previously, coimmunoprecipitates could be visualized only by radioactive amino acid incorporation in cell culture, whereas biotinylation and digoxigenination enable the study of specific protein expression in frozen tissues by immunoprecipitation and the visualization of coimmunoprecipitates. Chemolabeling presents the two major advantages of limiting the use of radioisotopes and allowing the use of frozen tissues in all types of protein expression studies.

Albumins↗
PubMed1994

Effects of the bradycardic agent ZD 7288 on membrane voltage and pacemaker current in sheep cardiac Purkinje fibres.

The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker i(f)-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated. ZD 7288 did inhibit i(f)-current. The i(f)-amplitude recorded with a 0.8s-lasting test pulse from about -50 mV to -100 mV was reduced to 50% of control at 0.85 mumol/l and to 5% of control at 10 mumol/l. The threshold potential of i(f)-activation was unaffected at a concentration of 1 mumol/l ZD 7288. The time constant of i(f)-activation at different test potentials was not changed by 1 mumol/l ZD 7288. The drug was equally effective during i(f)-activation with a 0.5 s-lasting test pulse applied at 0.05 Hz or 0.5 Hz. During long lasting (5 s) hyperpolarizing test pulses (-120 mV) the inhibition of i(f)-current was removed. In constantly stimulated Purkinje fibres (0.5 Hz) the slope of the early diastolic depolarization was decreased by ZD 7288. The half-maximal effect occurred at 0.92 mumol/l. There was strong correlation over the concentration range of 0.01 to 10 mumol/l ZD 7288 between the decrease of the slope of early diastolic depolarization and inhibition of i(f)-amplitude recorded with 0.8s-lasting test pulses to -100 mV. The correlation coefficient was r = 0.97. These results will explain the decrease in frequency of spontaneously active (about 0.6 Hz) Purkinje fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗