Biomedical subjects

S Poppema

Publications and source records attributed to S Poppema.

At least 37 records · Page 2Linked to original sources

PubMed2000

Frequent lack of translation of antigen presentation-associated molecules MHC class I, CD1a and Beta(2)-microglobulin in Reed-Sternberg cells.

Epstein-Barr virus (EBV) is present in Reed-Sternberg (RS) cells of a substantial proportion of Hodgkin's lymphoma cases. Most EBV-positive cases are also MHC class I-positive, whereas the majority of EBV-negative cases lack detectable levels of MHC class I expression. Application of the SAGE technique has led to the identification of tags corresponding to MHC class I and beta(2)-microglobulin genes in the EBV- and MHC class I-negative L428 Hodgkin's cell line. Further expression studies indicated that single RS cells that do not express HLA class I also lack beta(2)-microglobulins but frequently contain mRNA coding for these proteins. Another tag was identified corresponding to CD1a, a thymocyte and Langerhans cell antigen structurally related to the MHC class I genes. CD1a expression studies revealed mRNA in all cell lines and in several of the single cells, whereas immunostaining showed a cytoplasmic signal in only 2 of the 4 cell lines and in none of the Hodgkin's lymphoma tissue samples. In conclusion, RS cells frequently lack MHC class I, beta(2)-microglobulin and CD1a protein expression but contain mRNA coding for these proteins in some of the RS cells, suggesting a common mechanism affecting the translation of these antigen presentation-associated molecules.

Antigen Presentation↗

PubMed2000

Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas.

Recent studies provide evidence that Reed-Sternberg (R-S) cells produce factors that may explain the characteristic inflammatory infiltrate in the affected tissues of Hodgkin lymphoma. The various chemokines and cytokines that are produced lead to a preferential influx of Th2-type T cells and suppress Th1-type immune responses. Overall, the immunophenotype of the lymphocytes surrounding the R-S cells is consistent with anergic and/or Th2-type T cells. Therefore, these cells do not support a cytotoxic anti-tumor response. Since the R-S cells are neoplastic B cells, the cytokines produced by these T cells may in fact help their growth and/or survival. The production and induction of various other cytokines may also explain the influx of eosinophils (IL-5, eotaxin) and plasma cells (IL-6). Differences in chemokine and cytokine production may be responsible for the differences between the histological subtypes.

Cell Communication↗

PubMed2000

Clinical drug-resistant nodular sclerosing Hodgkin's lymphoma is associated with decreased bcl-2 expression in the surrounding lymphocytes and with increased bcl-2 expression in the Reed-Sternberg cells.

UNLABELLED: Identification of patients with Hodgkin's lymphoma who are primary refractory to chemotherapy will have great impact on treatment planning. Several studies have indicated that up-regulation of the bcl-2 proto-oncogene expression in non-Hodgkin's lymphoma can cause resistance to chemotherapeutic drugs. For this reason we investigated the relationship between expression of bcl-2, the pro-apoptotic protein Bax and MIB-1 with clinical drug-resistance in Hodgkin's lymphoma. METHODS AND RESULTS: Seven patients with nodular sclerosis Hodgkin's lymphoma under 40 years of age, who failed to achieve complete remission upon primary chemotherapy and 10 matched patients who did achieve complete response were selected from the Eindhoven Cancer Registry. Tissue sections from both groups of patients were stained for bcl-2, Bax and MIB-1. In the non-responding patients Reed-Sternberg cells expressed bcl-2 more frequently using a cut-off point of <25% to indicate negative cells (P = 0.04), whereas no differences were observed in the expression of Bax and MIB-1. In non-responding patients the lymphocytes surrounding Reed-Sternberg cells expressed bcl-2 less frequently (P = 0.002), using a cut-off point of < 25%, whereas no difference was observed in the expression of Bax and MIB-1. CONCLUSION: A high percentage of Reed-Sternberg cells expressing bcl-2 protein and a low expression of bcl-2 proteifi in the surrounding lymphocytes is associated with treatment-failure, and subsequent poor survival in young patients with nodular sclerosing Hodgkin's lymphoma. These results need further validation in larger studies.

Adolescent↗

PubMed2000

Management of side effects and complications in medical abortion.

Side effects are an expected part of medical abortion; some, such as pain and bleeding, result from the abortion process itself and are generally managed with orally administered analgesics and counseling. True medication side effects most commonly include nausea, vomiting, diarrhea, and warmth or chills. Complications of medical abortion usually represent an extreme or severe side effect. Large series have reported transfusion rates of <1%. Because of the infrequency of uterine instrumentation, postabortal endometritis appears to be rare with medical abortion. As with early surgical abortion, the clinician must remain aware of the possibility for ectopic pregnancy. Overall approximately 2% to 10% of patients will require surgical intervention for control of bleeding, resolution of incomplete expulsion, or termination of a continuing pregnancy. Understanding the types of side effects and complications that can occur will enable the clinician to counsel patients properly as well as to understand when medical intervention is necessary during the medical abortion process.

Abortifacient Agents↗

PubMed2000

Vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with acute lymphoblastic leukaemia (ALL).

We conducted a study to demonstrate vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with newly diagnosed acute lymphoblastic leukaemia (ALL). In five children, apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP-digoxigenin nick-end labelling (TUNEL) assay in blood samples collected during an up-front window study of vincristine monotherapy. In one patient, we found a striking increase of apoptotic cells from 2% (SEM 0.6) before to 40.7% (SEM 2.9) 3 h after vincristine injection. In the other patients, the maximum increase ranged from 0.8% to 4.3%. Wilcoxon matched pairs analysis of all patients confirmed that vincristine induces apoptosis in vivo in peripheral blood mononuclear cells in childhood ALL (P = 0.043).

Antineoplastic Agents, Phytogenic↗

PubMed2000

Spectrum of malignant lymphomas in Klang Hospital, a public hospital in Malaysia.

BACKGROUND: Lymphoma is a relatively common group of neoplasms diagnosed in hospital practice. This study aims to elucidate the pattern of this disease encountered in a public service hospital of the Ministry of Health, Malaysia. MATERIALS AND METHODS: A total of 98 biopsies from 92 patients were retrieved from the archives of Klang General Hospital, from January 1993 to June 1999. The histopathology of these biopsies were reviewed by two pathologists, and confirmed cases were sub-classified according to the WHO proposed scheme. Immunohistochemical staining with a panel of lymphoid antibodies was performed in aid of sub-typing. All cases were screened for Epstein-Barr virus association by in-situ hybridisation technique. RESULTS: 15 biopsies were excluded from further analysis due to inadequate material for further study or diagnosed as non-lymphoma. The remaining 83 biopsies were from 80 patients. 52 were males and 28 females. The male: female ratio was 1.9:1. There were 64 Malays, 4 Chinese and 12 Indians. The ages of patients ranged from 3 to 86 years with a mean age of 50.5 years. 73.8% of the diagnostic materials were nodal tissue. Fourteen patients had Hodgkin's lymphomas (HL), 6 being mixed-cellularity, 4 nodular-sclerosis, 1 lymphocyte-rich, 2 lymphocyte-depleted, 1 lymphocyte-predominant, and 66 had non-Hodgkin's lymphomas (NHL). The HL: NHL ratio was 1:4.7. Of the 66 cases of NHL, 9 (13.6%) were T- and 57 (86.4%) B-cell types. The most common NHL encountered was diffuse large B-cell type. Follicular-lymphoma constituted 16.7% of these NHL. 77.8% of T-NHL and 10.5% of B-NHL was EBV associated. Double staining of EBER with CD20 and EBER with CD3 in the T-NHL cases showed that in a majority of the cases, EBER-positive large cells did not express the T- or B- cell antigen. CONCLUSION: There is a relatively small proportion of T-cell lymphoma in this series of Asian patients. The reason is thought to be the lower utilisation rate of this hospital service by ethnic Chinese, as reflected by the hospital admission data.

Adolescent↗

PubMed1999

Serial analysis of gene expression: rapid RT-PCR analysis of unknown SAGE tags.

In a pilot study on SAGE on Reed-Sternberg cells we have sequenced 1055 tags representing 701 genes. Screening of the GenBank database resulted in the identification of a corresponding gene or EST for 490 of them. For 211 of the tags no homology could be detected. A major problem of the serial analysis of gene expression (SAGE) approach is how to further analyse the unknown tags. We have developed an RT-PCR-based method, rapid analysis of unknown SAGE tags (RAST-PCR), to analyse the expression of the corresponding genes. This approach can be used as a screening method to investigate whether or not the gene is differentially expressed between several cell types of interest.

Cell Line↗

PubMed1999

High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma.

Hodgkin's lymphoma is characterized by the combination of Reed-Sternberg (R-S) cells and a prominent inflammatory cell infiltrate. One of the intriguing questions regarding this disease is what is causing the influx of T lymphocytes into the involved tissues. We applied the serial analysis of gene expression (SAGE) technique on the Hodgkin's lymphoma-derived cell line L428 and on an Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cell line. A frequently expressed tag in L428 corresponded to the T-cell-directed CC chemokine TARC. Reverse transcription polymerase chain reaction analyses demonstrated expression of TARC in nodular sclerosis (NS) and mixed cellularity (MC) classical Hodgkin's lymphomas but not in NLP Hodgkin's lymphoma, anaplastic large-cell lymphomas, and large-B-cell lymphomas with CD30 positivity. Two of five cases of T-cell-rich B-cell lymphoma (TCRBCL) were TARC positive. RNA in situ hybridization (ISH) showed a strong signal for TARC in the cytoplasm of R-S cells, and immunohistochemical staining confirmed the presence of the TARC protein in the R-S cells of NS and MC Hodgkin's lymphomas. The lymphocytic and histiocytic (L&H)-type cells of nodular lymphocyte predominance Hodgkin's lymphoma and the neoplastic cells of non-Hodgkin's lymphomas with the exception of two cases of TCRBCL did not stain for TARC. TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes. The immunophenotype of lymphocytes surrounding R-S cells is indeed Th2-like, and by RNA ISH these lymphocytes showed a positive signal for the chemokine receptor CCR4. The findings suggest that production of TARC by the R-S cells may explain the characteristic T-cell infiltrate in classical Hodgkin's lymphoma.

B-Lymphocytes↗

PubMed1999

Low-dose mifepristone 200 mg and vaginal misoprostol for abortion.

The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women > or = 18 years, up to 8 weeks pregnant, and wanting an abortion. The women received 200 mg mifepristone orally, self-administered 800 micrograms misoprostol vaginally at home 48 h later, and returned 1-4 days later for ultrasound evaluation. Surgical intervention was indicated for continuing pregnancy, excessive bleeding, persistent products of conception 5 weeks later, or other serious medical conditions. Of the 933 subjects, 906 (97%) had complete medical abortions, 22 had surgical intervention, two were protocol failures, and three were lost to follow up. Of the 746 subjects who had no or minimal bleeding before misoprostol, 80% bled within 4 h and 98% within 24 h of using misoprostol. By day 7, 95% of women had a complete abortion. Side effects were aceptable in 85% of subjects, and 94% found the procedure acceptable. Low-dose mifepristone followed by vaginal misoprostol was highly effective as an abortifacient.

Abortifacient Agents, Nonsteroidal↗

PubMed1999

Cyclosporine inhibits long-term survival in cardiac allografts treated with monoclonal antibody against CD45RB.

BACKGROUND: We have previously reported that a monoclonal antibody to CD45RB is a novel immunosuppressive agent; however, the optimal regimen in cardiac allografts remains unknown. The present study was undertaken to determine the optimal protocol of this therapy and its interaction with cyclosporine. METHODS: A heterotopic heart allograft model was used in C57BL/6 to BALB/c mice. The following studies were conducted: 1) dose response study (low, intermediate, and high doses at 1, 3, and 9 mg/kg/day respectively), 2) short course (2 days) therapy vs. long course (9 days) therapy, 3) pretreatment (starting on day -1) vs no pretreatment, 4) daily therapy vs. alternative day therapy, and 5) monoclonal antibody treatment with and without cyclosporine. RESULTS: The efficacy of the CD45RB monoclonal antibody was dose and duration dependent (p<0.01). Pretreatment significantly improved the efficacy of this therapy (74.5+/-13.4 days vs. 30.6+/-1.5 days, p<0.01). Daily therapy was superior to alternate day therapy (74.5+/-13.4 days vs. 30.4+/-1.5 days, p<0.03). Interestingly, we found that administration of cyclosporine prior to, at the same time as, or after administration of the CD45RB monoclonal antibody had a detrimental effect on graft survival compared to mAb treated alone (16.6+/-0.4 days, 25+/-2.3 days, and 35.3+/-0.9 days respectively vs. 74.5 days, p<0.01). CONCLUSIONS: Immunosuppression with CD45RB monoclonal antibody is dose and duration dependent. Pretreatment and daily therapy improves results. Addition of cyclosporine inhibits long-term graft survival achieved by the monoclonal antibody alone.

Animals↗

PubMed1999

A monoclonal antibody, 3G12, reacts with a novel surface molecule, Hal-1, with high expression in CD30-positive anaplastic large cell lymphomas.

We established a monoclonal antibody, 3G12 (IgG1), with antiproliferative effects on a human T-cell leukaemia cell line, SUP-T13. Among haematolymphoid cell lines, 3G12 reacted with most T-cell lines, Epstein-Barr transformed B-cell lines, some myelomonocytic cell lines and, most strongly with an anaplastic large cell lymphoma (ALCL) cell line, Karpas 299. The cell panel reactive with 3G12 was similar, but not identical, to that of the anti-CD30 antibody Ber-H2. 3G12 induced Fas-independent apoptosis in SUP-T13 and it also induced growth-inhibition in a limited number of other cell lines, but not Karpas 299. Immunohistochemical studies on paraffin-embedded tissue specimens demonstrated that 3G12 reacted with most CD30-positive ALCL cases and some T-cell lymphomas and some Hodgkin's lymphomas, but not with B-cell lymphomas or non-haematogeneic tumours. The immunoprecipitation study with 3G12 demonstrated a major band of 200 kD and a minor band of 100 kD, which were different from CD30. Thus 3G12 defines a novel antigen that shares a similarity to CD30 in terms of distribution among haemopoietic cells. The data suggest that the 3G12-defined antigen, designated Hal-1, is important as a marker for ALCL and may play a role in its pathogenesis.

Animals↗

PubMed1999

Mechanisms of induction of renal allograft tolerance in CD45RB-treated mice.

BACKGROUND: Rejection is the most significant problem in the field of transplantation. The current goal of transplant immunology is to develop better immunotherapeutic protocols that are aimed at specifically suppressing alloreactivity and preserving an otherwise intact immune system. We have previously shown that mice will accept renal allografts indefinitely with normal renal function after two injections of a monoclonal antibody to the CD45RB protein. Furthermore, this antibody will reverse acute rejection when therapy is delayed until day 4 and will still induce tolerance. The mechanisms of this therapeutic benefit are not known. METHODS: BALB/C mice were used as recipients of major multiple histocompatibility complex-mismatched kidneys using C57BL/6 as donors. Immunoperoxidase microscopy and Northern blots for cytokine gene expression were used to study the renal allografts. Fluorescence-activated cell sorter (FACS) analyses of peripheral blood lymphocytes were performed. Phosphotyrosine peptide phosphatase assays were performed on splenic lymphocyte membranes. RESULTS: A CD45RB monoclonal antibody (MB23G2) induced tolerance and partially depletes peripheral blood lymphocytes. A therapeutically ineffective CD45RB monoclonal antibody (MB4B4) merely coated the circulating lymphocytes. Furthermore, MB23G2 stimulated more tyrosine phosphatase activity than MB4B4 in mouse T-cell membranes. CONCLUSIONS: The clearance of peripheral blood lymphocyte populations and stimulation of protein tyrosine phosphatase activity may be important in the mechanism of tolerance induction by CD45RB therapy, which may be clinically relevant in the therapy of organ rejection in humans.

Animals↗

PubMed1999

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗

PubMed1999

Immune reactions in classical Hodgkin's lymphoma.

The immune reaction in classical Hodgkin's lymphoma (HL) can be separated into an inflammatory response in the involved tissues and a generalized immune response in the patient. The local immune reaction in HL is by far the most prominent among all tumors, with the exception of so called T-cell-rich B-cell lymphoma, a subtype of large-cell B-cell lymphoma. The general immune response in patients with HL is best described as an acquired cellular immune deficiency, most likely a result of the presence of tumor, although some data in the literature suggest a preexisting immune deficiency. The cellular origin of Reed-Sternberg (RS) cells in classical and nodular lymphocyte-predominant HL is discussed elsewhere. RS cells and their mononuclear variants can be considered as clones of neoplastic B cells that, by secreting potent cytokines/chemokines, not only cause the symptoms of HL but also promote their own growth and evade immune surveillance. The characteristic histologic features of HL--the prominent inflammatory response, the influx of eosinophils, and the presence of fibrosis and sclerosis--may also result from the expression of a range of surface molecules and the production of cytokines and chemokines by RS cells.

Hodgkin Disease↗

PubMed1998

Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy.

CD45 is a family of transmembrane protein tyrosine phosphatases exclusively expressed by hematopoietic cells and critically involved in the regulation of T cell activation signals. We now demonstrate that three 100-microg doses of anti-CD45RB mAb MB23G2 can induce long-term engraftment of islets into major histcompatibility complex-disparate chemically diabetic mice. Long-term graft survivors (>120 days) were tolerant to new islet allografts from the original donor strain. MB23G2 induced a temporary decrease in number circulating leukocytes but had no effect on leukocyte number in other lymphoid compartments. Histologic examination of allografts from treated and untreated recipients revealed a similar peri-islet infiltration on day 6. Eleven days after transplant, the peri-islet infiltrate in treated animals persisted, but in marked contrast to untreated control animals, there was no insulitis and islet integrity was preserved. The peri-islet infiltrate from treated animals showed a mild increase in CD4 cells, a decrease in CD8 cells, and decreased intensity of CD45RB expression. Treatment of naive animals with anti-CD45RB (MB23G2) resulted in a shift in CD45 isoform expression on T cells with a loss of higher molecular weight isoforms and increased expression of lower molecular weight (CD45R0) isoform. This shift in CD45 isoform expression from CD45RBHi to CD45RBLo was associated with an increase in the intragraft expression of transcripts for interleukin (IL) 4 and IL-10, consistent with the expected activity of this distinct immunoregulatory T cell subset. Antibody-mediated targeting of CD45 may induce tolerance through novel mechanisms and have direct applicability to clinical transplantation in humans.

Animals↗

PubMed1998

Ischaemic colitis and lung infiltrates caused by extramedullary haematopoiesis in a patient with an acute erythroid leukaemia following polycythaemia vera.

A patient with 'spent' polycythaemia vera showed extensive extramedullary haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory investigation, the EMH also included immature erythroblasts due to acute erythroid leukaemia. It is hypothesised that the abnormal homing of erythroid progenitors might be related to the abnormal expression of antigens, such as CD36.

Aged↗

PubMed1998

Immune escape mechanisms in Hodgkin's disease.

BACKGROUND: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's disease are histologically characterised by a small population of neoplastic cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS cells) and an extensive admixture of other cell types including lymphocytes, plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is largely known, but the mechanisms and functional effects are not. The small lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that express early activation markers. The absence of prominent specific cytotoxic T cell or natural killer (NK) cell populations seems to argue against a Th1-type response, whereas the sometimes prominent admixture of plasma cells and eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell population may result from selective influx of CD4 T cells or from selective depletion of CD8 and NK cells. RESULTS AND DISCUSSION: The T cells surrounding RS cells have an immuno-phenotype and cytokine production capability consistent with a Th2-type response. RS cells express several members of the TNF receptor family such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS expressing, CD8+ T cells and NK cells. The RS cells also produce TGF beta and interleukin-10 that may downmodulate the Th1 response. In addition, the Reed-Sternberg cells produce the chemokine TARC that could lead to the specific attraction of a Th2 T-cell subset. CONCLUSION: RS cells have several mechanisms that may allow it to escape an effective immune response. The relative contributions of each of these and other potential mechanisms are not yet known.

CD4 Antigens↗

PubMed1998

Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma).

Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma, anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified.

Diagnosis, Differential↗