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J Lorenzen

Publications and source records attributed to J Lorenzen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas.

The expression of MUC1 and MUC2 mucin peptide core antigens in gastric carcinomas was studied by immunohistochemistry to determine correlations with TNM stage and histo-pathological classifications as well as a possible prognostic impact. Paraffin-embedded specimens from 128 gastric carcinomas with a minimal follow-up of 5 years were immunostained. In addition to a polyclonal antiserum generated against polymorphic epithelial mucin (MUC1) from human milk, 2 monoclonal antibodies (MAbs), HMFG2 (anti-MUC1) and 4FI (anti-MUC2), were applied. Reactivity of carcinomas was correlated with the classifications of the UICC (TNM), WHO and Laurén. Correlations with overall survival were analyzed using the Kaplan and Meier product limit method. MUC1 immunoreactivity was associated with an advanced pTNM stage. The demonstration of both mucin species (MUC1, MUC2) displayed a statistically significant correlation with tubular/papillary vs. signet-ring cell differentiation as well as with intestinal-type vs. diffuse-type of tumor growth according to Laurén. In particular, MUC2 was only rarely detectable in signet-ring cell and diffuse-type tumors. MUC1 correlated with poor prognosis in all cases and the subgroup of stage I tumors. According to the histopathological classifications, a similar result was observed in signet-ring cell and diffuse-type carcinomas. In contrast, MUC2 reactivity was associated with a favourable prognosis of intestinal-type carcinomas. In the non-neoplastic gastric mucosa, both peptide cores were recognized in the superficial epithelium, whereas parietal cells contained only MUC1, and intestinal metaplasia almost exclusively MUC2 antigens. We conclude that the mucin peptide core antigens are suitable markers for the tubule-rich gastric carcinomas, which may in part be derived from intestinal metaplasia. In addition, MUC1 may exert a prognostic relevance and appears to be involved in the progression of diffuse-type tumors.

Adult↗
PubMed1998

Detection of the bcr/abl gene in bone marrow macrophages in CML and alterations during interferon therapy--a fluorescence in situ hybridization study on trephine biopsies.

A fluorescence in situ hybridization (FISH) study was performed on trephine biopsies of the bone marrow in chronic myelogenous leukaemia (CML) to evaluate the bcr/abl translocation in macrophages before and during interferon (IFN) therapy. Mature macrophages and osteoclasts were identified by the monoclonal antibody PG-M1, which recognizes a fixative-resistant epitope of the CD68 molecule. In contrast to a control group, in 145 of 479 (30 per cent) macrophages of the CML bone marrow, a positive fusion signal was found, together with corresponding translocation sites in the surrounding myeloid cells. In patients following IFN treatment for approximately 12 months and with haematological/cytogenetic remission by clinical standards, this number was reduced to 10 of 136 (9 per cent) macrophages. In addition, the few multinucleated osteoclasts of the untreated CML bone marrow displayed positive translocation spots. This finding supports the hypothesis that stromal macrophages and osteoclasts are of haematogenic stem cell origin. Moreover, clinical remission and reduction of bcr/abl-positive macrophages under IFN therapy lend support to the hypothesis that the presence of malignant stromal macrophages may contribute to the selective expansion of leukaemic precursors and the suppression of normal haematopoiesis in CML.

Antigens, CD↗
PubMed1998

[Renal angiomyolipoma as a rare cause of retroperitoneal hemorrhage].

Angiomyolipomas are hamartomas that may be found sporadically or associated with tuberous sclerosis (M. Bourneville-Pringle). Clinically, this long-term asymptomatic tumor becomes evident as an acute retroperitoneal hemorrhage or by symptoms of a flank mass. Due to the high percentage of fat components in this tumor type, computed tomography is far superior to other radiological procedures. In view of two of our own case reports, the therapeutic strategies are discussed, paying regard to the actual literature in this field.

Adult↗
PubMed1998

Apoptosis and expression of bcl-2 protein are inverse factors influencing tumour cell turnover in primary carcinoid tumours of the lung.

AIMS: This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were analysed in a search for associated biological parameters. METHODS AND RESULTS: The in-situ end-labelling technique (ISEL) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. In contrast, bcl-x was observed predominantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carcinoid tumours failed to show a staining for p53, p21/waf. p27 and mdm-2 proteins. CONCLUSIONS: The different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.

Adult↗
PubMed1998

Biosensor determination of the microscale distribution of nitrate, nitrate assimilation, nitrification, and denitrification in a diatom-inhabited freshwater sediment

High-resolution NO3- profiles in freshwater sediment covered with benthic diatoms were obtained with a new microscale NO3- biosensor characterized by absence of interference from chemical species other than NO2- and N2O. Analysis of the microprofiles obtained indicated no nitrification during darkness, high rates of nitrification and a tight coupling between nitrification and denitrification during illumination, and substantial rates of NO3- assimilation during illumination. Nitrification during darkness could be induced by purging the bulk water with O2 gas, indicating that the stimulatory effect on nitrification by illumination was caused by algal production of O2. NH4+ addition did not stimulate nitrification during darkness when O2 was restricted to the upper 1-mm layer, and there was thus a low nitrification potential in the permanently oxic top 1 mm of the sediment.

Journal Article↗
PubMed1998

[Chest X ray: routine indication in the follow-up of differentiated thyroid cancer?].

AIM: This retrospective study sought to elucidate whether routine chest x-ray is still useful for detection of pulmonary metastases in low risk patients despite the high sensitivity of the tumor marker thyroglobulin. METHOD: The hospital files of 609 patients with well-differentiated thyroid cancer were analysed. Pulmonary formation of metastases was diagnosed in 50 patients. The thyroglobulin value at the time of diagnosis was compared with the chest x-ray findings and, if present, additional diagnostic information such as Iodine-131 whole body scintigraphy (WBS) and thorax CT. RESULTS: The sensitivity of the chest x-ray to detect pulmonary metastases was at 52% lower than that of WBS (64%), thorax CT (82%) and thyroglobulin during suppression therapy (86%). Among the patients with papillary carcinoma stage I and II (UICC 1987), only 1 patient developed pulmonary metastases during follow up. In this low risk group of patients, detection of lung metastases exclusively by chest x-ray, without elevation of thyroglobulin level is extremely rare (calculated probability 1/4000) and associated with considerable costs. CONCLUSION: Routine, life long chest x-ray in low risk patients without a suspected recurrence (e.g. positive thyroglobulin) needs to be reconsidered.

Carcinoma, Papillary↗
PubMed1997

Prevention of Epstein-Barr virus-induced human B-cell lymphoma in severe combined immunodeficient mice treated with CD3xCD19 bispecific antibodies, CD28 monospecific antibodies, and autologous T cells.

Bispecific CD3 x antitumor antibodies in combination with coactivating CD28 antibodies can induce resting T cells to proliferate and to lyse syngeneic tumor cells (M. Azuma et al., J. Immunol., 150: 2091-2101, 1993; M. Azuma et al., J. Exp. Med., 177: 845-850, 1993). This combination of antibodies may therefore be useful for active immunotherapy of malignant tumors. In this study, we present a preclinical model to evaluate CD3xCD19 bispecific antibodies. We investigated whether bispecific antibodies prevent the development of malignant EBV-induced lymphomas in severe combined immunodeficient (SCID) mice which lack functional B and T lymphocytes (G. C. Bosma et al., Immunogenetics, 29: 54-57, 1989). SCID mice were engrafted (i.p.) with peripheral blood lymphocytes and EBV and treated after 3 days with CD3xCD19 bispecific antibodies and CD28 antibodies. Our data demonstrate that the growth of B cell lymphomas can be prevented in SCID mice by treatment with CD3xCD19 bispecific antibodies and that B-lymphoma-specific T cells can be recruited. In contrast to in vitro experiments, there was no clear effect of CD28 administration which is due to high expression of B7-1 on the transplanted B cells. Lymphoma-bearing mice had elevated titers of interleukin10 in the serum, in contrast to tumor-free animals. As shown by PCR analysis, there was no evidence of dormant B-lymphoma cells in specimens from surviving mice. In the spleen of surviving mice, rearranged human T-cell receptor gamma gene segments were detectable. Furthermore, mice that were initially treated with CD3xCD19 and CD28 antibodies did not develop lymphomas upon rechallenge with EBV-infected mononuclear cells of the same donor, whereas control animals did. Our results obtained from this autologous human B-lymphoma model have implications for the design and evaluation of new immunotherapeutic modalities for the treatment of human B-cell lymphoma with bispecific antibodies.

Animals↗
PubMed1997

Apoptosis and proliferation (PCNA labelling) in CML--a comparative immunohistological study on bone marrow biopsies following interferon and busulfan therapy.

A comparative morphometric analysis was performed on smears and trephine biopsies of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the effects of therapy on apoptosis and cell proliferation. The in situ end-labelling (ISEL) technique was used for the demonstration of programmed cell death, in combination with the monoclonal antibody PG-M1 to identify macrophages. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). In CML (48 patients), significantly higher rates of apoptosis were observed than in normal bone marrow (smears, frozen sections, and paraffin-embedded samples) of 15 patients. In contrast, the PCNA labelling index of CML was not different from controls. In bone marrow tissue derived from CML patients, about 36 per cent of apoptotic bodies were ingested with CD68-positive macrophages. Study of the histotopographical distribution of labelled cells revealed that in CML, in contrast to the normal bone marrow, programmed cell death and PCNA activity were concentrated along the paratrabecular generation zone. In 28 patients with CML treated with interferon (IFN), sequential trephine biopsies displayed a significant enhancement of apoptosis which was associated with a decrease in PCNA reactivity. In contrast to this finding, no such alterations could be observed in 24 patients who received busulfan (BU) monotherapy. This study furthers the understanding of cell kinetics in CML. IFN therapy induces apoptosis and suppresses cell proliferation. The rate of programmed cell death prior to therapy and the extent of IFN-triggered apoptosis exert a significant predictive impact on survival. In this study, ISEL-positive (apoptotic) cells and bodies do not correspond to unscheduled cell repair as detected by PCNA immunoreactivity.

Adult↗
PubMed1997

The mummified Hodgkin cell: cell death in Hodgkin's disease.

This study attempts to define more clearly the morphology and ultrastructure of mummified Hodgkin cells, to determine their incidence in the different histological subtypes of Hodgkin's disease (HD), and to correlate these data with the expression of p53, bcl-2, mdm2, and p21/WAF1. Forty-five cases of primary HD were examined at light and electron microscopic level. DNA strand breaks were detected by the in situ end-labelling (ISEL) and the TdT-mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique. Mummified Hodgkin cells display morphological features that differ from those of classical apoptosis. In contrast to apoptotic cells, mummified Hodgkin and Reed-Sternberg (HRS) cells do not react in the ISEL or TUNEL procedures and maintain the expression of antigens such as CD30 and CD15. The morphology of mummified tissue cells could be simulated by CD95-mediated induction of apoptosis in the Hodgkin cell line HDLM2 if internucleosomal DNA fragmentation was inhibited by zinc ions. The highest incidence of mummified cells was found in the nodular sclerosis and mixed cellularity subtypes, whereas the lowest frequency was observed in nodular paragranuloma. The frequency was independent of p53, bcl-2, p21, and mdm2 expression. p21 and mdm2 immunoreactivity of HRS cells was correlated with p53 status. HRS cells in nodular paragranuloma were virtually negative for p21/WAF1 or bcl-2. Classical apoptotic cells reacting in the TUNEL and ISEL procedures are found in all subtypes of HD and are derived from the non-neoplastic cellular background. In conclusion, mummified Hodgkin cells display features of apoptosis lacking the internucleosomal DNA fragmentation. The pattern of the p53-transactivated genes mdm2 and p21/WAF1 suggests that inactivating mutations of p53 are rare in HD.

Adolescent↗
PubMed1997

Incidence of apoptosis in HIV-myelopathy, myelodysplastic syndromes and non-specific inflammatory lesions of the bone marrow.

Myelodysplastic syndromes, AIDS-related myelopathy and non-specific inflammatory reactions (mostly rheumatoid myelitis) are characterized by normo- to hypercellular bone marrow, but frequently display cytopenias in the peripheral blood. In the current study we have addressed the question whether this situation reflects an increased programmed cell death in haemopoiesis. For this purpose, the in situ end-labelling technique was applied to formalin-fixed and paraffin-embedded trephine biopsies derived from patients and a control group without any haematological disorder. Results were evaluated by morphometry. Significantly more apoptotic cell death was observed in the haemopoietic marrow of patients with either disease. Using double-immunohistochemistry with the monoclonal antibody PG-MI (CD68), we were able to demonstrate that approximately one third of the apoptotic cells were ingested by macrophages. Our findings are in keeping with previously published data that postulated increased frequencies of macrophages in these disorders as well as raised serum levels of TNF-alpha.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Apoptosis (programmed cell death) in idiopathic (primary) osteo-/myelofibrosis: naked nuclei in megakaryopoiesis reveal features of para-apoptosis.

There is general agreement that apoptosis (programmed/physiological cell death) plays an important role in regulating normal hematopoiesis and that so-called naked nuclei (NN) present end stages of megakaryopoiesis. Using in situ end-labeling techniques (ISEL), a morphometric analysis was performed on bone marrow trephine biopsies repeatedly derived from patients with idiopathic (primary) osteo-/myelofibrosis (IMF). The purpose of this study was to quantify apoptosis and to elucidate its relationship with NN of megakaryopoiesis. Moreover, evolution of this phenomenon during progression of myelofibrosis (assessed by morphometry of silver-stained sequential biopsies) and its predictive value were investigated. In IMF, morphometric measurements revealed a rate of ISEL-positive cells that was significantly higher than previously published data on the normal bone marrow and in patients with acute myeloblastic leukemia, but lower than in the myelodysplastic syndromes. However, NN with their tightly packed (nuclear) lobules and condensed chromatin were not reactive. Statistical evaluation failed to show a significant correlation between incidence of apoptotic cells and fiber density or an increase in this feature associated with progression of fibro-osteosclerotic marrow changes and prognosis. The failure of NN to react in ISEL implicates an absence of DNA fragmentation characteristic of apoptosis. For this reason our findings are in keeping with the assumption that NN are compatible with para-apoptosis.

Apoptosis↗
PubMed1996

Depth of infiltration of primary gastric B-cell lymphomas--correlations with proliferation, apoptosis and expression of p53 and bcl-2.

Local extension has been shown to be a major prognostic factor in primary gastric B-cell lymphoma. In order to evaluate whether this parameter might be correlated with cell proliferation or its regulation, a retrospective study was performed. Fifty-three surgical specimens with primary gastric B-cell lymphomas were analysed concerning histological grading, depth of infiltration and Ann-Arbor stage. In addition, immunohistochemistry (p53[Do7], bcl-2[bcl-2-124], Ki-67 [MiB1]) and in situ end-labeling (apoptotic bodies) were applied. The depth of infiltration was significantly correlated with Ann-Arbor stage (p < 0.001) and histological grading (p < 0.002). Furthermore, the semiquantitatively evaluated expressions of Ki-67, apoptotic bodies and p53 revealed that tumours limited to the mucosa and submucosa had lower numbers of stained cells than lymphomas infiltrating the muscularis propria or beyond (p < 0.001 in all cases). Analysis of bcl-2 expression showed an inverse picture (p < 0.05). The importance of local spread of gastric lymphomas is underscored by our findings: in gastric lymphomas infiltrating the muscularis propria or beyond, powerful proliferative stimuli have been acquired, e.g. associated with p53 mutations, that are independent of the known mucosa-associated stimuli, Helicobacter pylori and auto-immunity.

Apoptosis↗
PubMed1996

[Comparison of CT arterioportography and spiral CT arterioportography in malignant lesions of the liver].

PURPOSE: To determine the value of spiral CT during arterial portography (SCTAP) in detecting and localising focal liver lesions we compared the SCTAP findings to those gained by conventional CT during arterial portography (CTAP). MATERIAL AND METHODS: We evaluated a total of CT scans of 128 patients with 162 malignant lesions of the liver. 45 patients underwent SCTAP and 83 patients CTAP. Results of radiological studies were compared with surgical and pathological findings. RESULTS: The overall sensitivity of SCTAP was 93% with a sensitivity of 80% for lesions of less than 1 cm diameter. For CTAP the overall sensitivity was 88%, but the sensitivity for lesions smaller than 1 cm was only 53%. Although with SCTAP examination of hepatic vasculature and liver parenchyma was continuous, we found no advantage in the localisation of lesions to the liver segments compared to CTAP, and the sensitivity of localisation did not correlate with the size of lesions. CONCLUSION: In our study SCTAP turned out to be a reliable radiological method in the preoperative detection of focal liver lesions, with a high overall sensitivity. SCTAP showed improved sensitivity in the detection of small malignant lesions (< 1 cm) in comparison to CTAP.

Adult↗
PubMed1996

Effect of interferon therapy on bone marrow morphology in chronic myeloid leukemia: a cytochemical and immunohistochemical study of trephine biopsies.

The effect of interferon (IFN) therapy on bone marrow features in chronic myeloid leukemia (CML) has been studied on successive trephine biopsies (mean interval 13 +/- 8 months) by cytochemical and immunohistochemical methods in combination with morphometry and in comparison with a control group of patients who received monotherapy by busulfan (BU). Following IFN administration (IFN-alpha frequently in combination with IFN-gamma), there was a decrease in neutrophil granulopoiesis accompanied by a significant expansion of erythroid precursors and increased numbers of hemosiderin-laden macrophages. These changes corresponded with the hematologic response in 21 of the 25 patients investigated. Numbers of megakaryocytes and reticulin/collagen fiber density increased during treatment. Most conspicuously, in responding patients atypical micromegakaryocytes, usually characterizing CML, were partially replaced by normal-sized cells of this lineage. These features are in keeping with the assumption of a reappearance of the normal hematopoietic cell clone as the result of IFN therapy, which was not found in the BU-treated control group. On the other hand, a relevant subpopulation of micromegakaryocytes (about 30%) was still maintained. This result probably relates to the failure to improve myelofibrosis more effectively. Analysis of cell proliferation (proliferating cell nuclear antigen-PCNA) and apoptosis (in situ end labeling) revealed a reduction in PCNA labeling and increased numbers of cells undergoing programmed death. Identification of the activated subset of macrophages (alpha-D-galactosyl residues expression) by appropriate lectin histochemistry disclosed an increase in the number of GSA-I binding cells. These findings were exclusively limited to IFN administration and reflect an inhibitory effect of IFN on cell proliferation and stimulation of programmed cell death. The latter phenomenon probably results in increased phagocytosis of clonally transformed myeloid cells by GSA-I-positive (activated) macrophages.

Adult↗
PubMed1996

Single-cell analysis of T-cell receptor-gamma rearrangements in large-cell anaplastic lymphoma.

Large-cell anaplastic lymphomas (LCAL) are characterized by their distinctive morphology together with expression of the CD30 antigen. In addition, a chromosomal translocation, t(2;5) (p23; q35), can be detected in most cases. A significant proportion of LCALs carry rearrangements of the T-cell receptor-gamma (TCR-gamma) locus and display a T-cell phenotype. In about a third of the cases, another type of non-Hodgkin-lymphoma precedes LCAL. Early transformations of non-Hodgkin's lymphoma into LCAL might escape clinical detection in a significant number of cases. The existence of clonally related lymphoid cells within the lymph node infiltrates must be claimed in these cases. Recently, a small-cell-predominant variant of LCAL was described in which only few large tumor cells expressing the CD30 antigen are found together with numerous small lymphocytes, which are frequently CD30-. This observation in particular prompted us to investigate the clonal relationship of the tumor cell compartment and admixed small lymphocytes in one case of common LCAL with T-cell genotype. For this purpose, we chose to amplify rearranged TCR-gamma sequences from single cells isolated from immunostained frozen sections by using a micromanipulator. A total of 119 cells were investigated. Amplification products were obtained in 17 of 79 CD3+ cells, 12 of 30 CD30+ cells, and three of 10 CD20+ cells. The nucleotide sequences were determined in 28 cells by nonradioactive sequencing. In 11 CD30+ cells, the predominant rearrangement of TCR-gamma was identified. No clonal diversity was observed. The small CD3+ lymphocytes were unrelated to the anaplastic CD30+ tumor cells. This report describes a method to analyze rearrangements of the TCR-gamma in single cells isolated from immunostained frozen sections. Application of this technique revealed an absence of clonal diversity in a case of LCAL and documented the polyclonal nature of admixed small CD3+ lymphocytes.

Cell Separation↗