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Biomedical subjects

J Jansen

Publications and source records attributed to J Jansen.

At least 235 records · Page 13Linked to original sources

The effect of anticoagulant on the cell size of hairy cells and other malignant hematologic cells. A study with the Hemalog D.

The size of blood cells can be influenced by anticoagulants, especially the EDTA derivatives. The Hemalog D differential counter was used in the diagnosis and follow-up of hairy cell leukemia. The percentage of large unstained cells (LUC) closely correlated with the percentage of hairy cells. However, there was a highly reproducible rapid decrease in LUC during the period of time after collection of the blood, when potassium EDTA was used as an anticoagulant. This "loss" in LUC could not be attributed to a selective disappearance of hairy cells, but to a shift into the lymphocyte box. The steep decline did not occur when sodium EDTA was used. The phenomenon seems to be specific for hairy cells, as it was not observed, or was considerably less obvious in other lymphocytic and non-lymphocytic leukemic malignancies.

Anticoagulants↗

Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effect on circulating T lymphocytes.

Eight recipients of a bone-marrow graft from HLA-identical, MLR-nonreactive sibling donors who had developed grade II-IV acute graft-versus-host disease (aGVHD), were given 14 consecutive daily injections of 5 mg of a murine anti-T-cell monoclonal antibody (MCA) called OKT3. Four patients with grade II aGVHD showed a complete response; two patients with grade II had a partial response, and two patients (one with grade II and one with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the first injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence, and flow cytometry. Circulating T3+ T cells dropped to virtually zero within 1 hr following the first injection. Low numbers of E-rosetting cells were still demonstrable during OKT3 therapy. During the second week of treatment, T-cell markers (T3, T4, T8) started to increase again, in spite of excess antibody in the circulation. At that time, T cells showed weaker fluorescence with OKT3 than before OKT3 therapy, suggesting modulation of the T3 antigen. After cessation of OKT3 therapy, T cells reached pretreatment levels within one week. None of the six patients studied developed anti-mouse-Ig antibodies. These results suggest that OKT3 therapy is effective in limited aGVHD. The absence of anti-mouse-Ig antibody formation may allow repeated courses of MCA that may add to their therapeutical potential.

Acute Disease↗

Prognostic factors in IgD myeloma: a study of 21 cases.

A series of 21 patients with IgD myeloma was studied retrospectively, to assess which parameter present at the time of diagnosis was of prognostic importance for survival and whether the clinical staging system of Durie and Salmon had predictive value for the survival time of these patients. Survival time did not appear to be correlated with haemoglobin concentration, thrombocytopenia, initial level of M-protein, amount of Bence-Jones proteinuria, hypercalcaemia, serum creatinine level, presence of osteolytic lesions or hepatosplenomegaly. Neither did the staging system of Durie and Salmon predict the survival time. It is concluded that clinical staging is of limited value in the management and prediction of the survival time of IgD myeloma patients.

Adult↗

The in vitro growth pattern of human bone marrow in methylcellulose stimulated by different concentrations of conditioned medium.

The proliferation of human bone marrow in methylcellulose stimulated by various concentrations of conditioned medium (CM) and observed at various intervals was studied. The growth kinetics of granulocytic aggregates was found to differ from monocytic clusters and colonies. Granulocytic aggregates showed a consistent and reproducible dose-response relationship; at day 7, the maximum number of granulocytic aggregates was found at 4% CM. At higher levels, the total number of aggregates decreased, while the number of cells per aggregate increased. The number of macrophage aggregates was far less, depending on the CM concentration. Photographic interval studies showed that at high concentrations of CM, clusters and colonies were formed earlier, but also coalesce to form one colony. Our results suggest that the proliferation kinetics of granulocytic aggregates are complex and preclude simple statements about sensitivity to colony-stimulating activity.

Bone Marrow↗

The effect of liposomal charge on the neutralizing antibody response against inactivated encephalomyocarditis and Semliki Forest viruses.

The primary neutralizing antibody response to encephalomyocarditis (EMC) virus and Semliki Forest virus (SFV) is enhanced by addition of either negatively or positively charged liposomes. The purified u.v. light inactivated viruses were merely mixed with liposomes and injected intraperitoneally (i.p.) into mice. In contrast, neutral liposomes were unable to enhance the primary response to these viruses. Furthermore primary immunization with inactivated SFV mixed with either neutral, positively or negatively charged liposomes was associated with an enhancement of the secondary humoral response after i.p. booster injection of mice with inactivated virus alone. But neutral liposomes seemed to be less effective in this respect than either positively or negatively charged liposomes.

Animals↗

Polymorphic and monomorphic HLA-DR determinants on human hematopoietic progenitor cells.

The expression of monomorphic Ia-like antigens and polymorphic (allotypic) HLA-DR determinants on CFU-GM, BFU-E, CFU-E, and CFU-GEMM was studied in bone marrow and peripheral blood cells from normal healthy individuals. Using various polyclonal and monoclonal anti-Ia-like antibodies, the presence of HLA-DR backbone antigens was shown on all hematopoietic progenitor cells (HPC) studied, both in complement-dependent cytotoxicity assays and in fluorescence-activated cell sorting (FACS). The expression of allotypic determinants was demonstrated on all HPCs, using the HLA-DR typing sera anti-HLA-DR1, 2, 3, 4, 5, and 7. The Class II antigen MT-2 was also shown on all HPCs, using both monoclonal and alloantisera, whereas the MB-1 (DC-1) determinant could not be demonstrated on HPCs. This might open the possibility of removing MB-1-positive malignant cells from the graft in autologous bone marrow transplantation.

Antilymphocyte Serum↗

Immunohistochemical studies of the spleen in hairy-cell leukemia.

Immunohistochemical studies of 10 spleens from patients with hairy-cell leukemia (HCL) with a battery of monoclonal and heterologous antibodies were performed in order to obtain information on the phenotype of the neoplastic cells and the admixture of reactive cells. The hairy cells (HCs) were shown to react with several anti-B-cell antibodies (Y29/55, Leu10, HLA-DR), but only a minority of cases showed reactivity with antibody BA-1. The cells of all cases were nonreactive with anti-T and/or anti-macrophage antibodies. In contrast with cell-suspension studies, in immunohistochemical studies the HCs did not react with antibody OKM1. The reactive T-lymphocytes showed a shift toward T helper cells in the red pulp, but not in the white pulp. It was confirmed that "pseudosinuses" and "bloodlakes" are outlined by HCs and not by sinus-lining cells: the lining cells of the blood lakes were Y29/55+ and Leu10+, but negative with antibodies known to react with sinus-lining cells (Leu2a, BA-2). These data suggest that immunohistologic studies of the spleen in patients with HCL can be helpful in differential diagnosis and can provide information concerning the reaction of splenic tissue to the infiltration by hairy cells.

Antibodies, Monoclonal↗

Complement-dependent cytotoxicity in the analysis of antigenic determinants on human hematopoietic progenitor cells with HLA-DR as a model.

Complement-dependent cytotoxicity (CDC) assays using anti-Ia antisera have resulted in controversial conclusions about the expression of HLA-DR determinants on human hematopoietic progenitor cells (HPC). The expression of these antigens on CFU-E in particular could often not be demonstrated. Since this is contradictory to our own results, we decided to study the influence of both the antibody and complement concentrations in CDC assays using murine monoclonal and polyclonal anti-Ia (HLA-DR "backbone") antibodies and human anti-HLA-DR typing sera. We found that with use of the same anti-Ia antibody concentrations, elimination of CFU-E required significantly more complement than CFU-GM and BFU-E. In CDC assays with antipolymorphic HLA-DR antisera, complete kill of both CFU-E and BFU-E required significantly more complement than of CFU-GM. Insufficient complement concentration could be partly overcome by increasing the antibody concentration. Intrinsic insensitivity of CFU-E to low concentrations of complement could be excluded by experiments using monoclonal anti-HLA-A/B/C "backbone" antibodies. Furthermore, FACS experiments demonstrated that the density of HLA-DR determinants on CFU-E is lower than on BFU-E and CFU-GM. These data show that in CDC assays, antigens with low expression on HPC can easily be overlooked.

Colony-Forming Units Assay↗

Hairy cell leukemia: its place among the chronic B cell leukemias.

Hairy cell leukemia is a chronic B cell leukemia. The presence of surface Ig (SIg) of gamma or multiple isotypes on the cells locates HCL at a rather mature stage of B cell differentiation. The reactivity of HC with McAb is in accordance with this concept (T65-, OKM1+, FMC7+, BA-1-). To relate HCL to other chronic B cell leukemias, a morphologic classification was developed that distinguishes, besides HCL, five subtypes of chronic B cell leukemia. CLL showed weak staining for SIg of mu +/- delta class. The phenotype with McAb was T65+, OKM1-, FMC7-, BA-1+. Prolymphocytic transformation of CLL had essentially the same membrane phenotype. LPL often had brighter SIg of mu +/- delta class with gamma or multiple isotypes in about half of the cases. McAb gave a T65-or+, OKM1-or+, FMC7-or+, BA-1+ phenotype. The same surface-marker profile was found in CL. Finally, PLL showed bright SIg of gamma or multiple isotypes in the majority of cases and reactivity with McAb according to a T65-or+, OKM1+, FMC7+, BA-1+ pattern. The various immunologic phenotypes of the morphologic subtypes showed a considerable overlap. The various chronic B cell leukemias should be located in the scheme of B cell differentiation in the sequence CLL-LPL/CL-PLL-HCL.

Antibodies, Monoclonal↗

T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease.

Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4-7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.

Adolescent↗

Surface bound or cytoplasmic immunoglobulins: interpretation of the immunofluorescence observed in cytocentrifuge slides of human lymphocytes.

Results of immunofluorescence observations in the study of normal and malignant blood lymphocytes are described. Data which support the proposition that most membrane bound immunoglobulin molecules are stable enough to remain intact during cytocentrifuge slide preparation are presented. Therefore not all positive cells in a fixed cytocentrifuge slide should be considered as containing cytoplasmic immunoglobulins. A correct interpretation is essential because of its bearing on our concepts of B lymphocyte differentiation.

B-Lymphocytes↗

Prognostic significance of immunologic phenotype in hairy cell leukemia.

Hairy cell leukemia (HCL) is a usually chronic B cell lymphoproliferative disorder. To evaluate the prognostic significance of the various heavy and light chain determinants of the surface immunoglobulins (slg), we analyzed the clinical data and immunologic phenotype of 64 patients with HCL. Sixty-two of the 64 patients showed slg, which was invariably of only one light chain type (kappa 33, lambda 29). The actuarial survival of the cases expressing kappa-light chains was significantly better than those with lambda-light chains (p less than 0.002). This difference persisted when only cases with gamma or alpha gamma heavy chains were considered. No differences between the kappa and lambda-subgroups were discovered with respect to parameters of clinical importance. The various heavy chain classes of slg did not correlate significantly with the survival time. These results suggest that the immunologic phenotype, in particular the light chain type, may be a prognostic factor in patients with HCL.

Adult↗

Inhibited development of cyathostominae in the horse in the early third stage.

Inhibited early third stage larvae of Cyathostominae were found in the digested mucosa of the large intestine of 12 yearling, female Shetland ponies, which were used in two grazing experiments. The ponies were killed in late autumn. In some ponies the inhibited larvae were very abundant and in most animals the majority of the Cyathostominae populations consisted of these early third stage larvae, suggesting that the phenomenon has an epidemiological significance.

Animals↗

Factors influencing platelet survival during antilymphocyte globulin treatment.

The antiplatelet effect of antilymphocyte globulin (ALG) was studied during 49 courses of therapy of 4-5 d given to 43 patients with severe aplastic anaemia. Concomitant corticosteroid therapy was usually given in moderate ( MDC ) dosages from 10 to 30 mg daily (40 courses); in nine courses the ALG infusions were combined with high dose (20 mg/kg) methylprednisolone (HDC). Clinical side effects were mainly seen during the first ALG infusion. In all MDC -treated patients a decrease of the peripheral-blood leucocyte count to 20-30% of the pretreatment level during the first ALG infusion was associated with a severely shortened platelet survival. During subsequent infusions, which were tolerated much better, the survival of transfused platelets increased considerably. In the HDC-treated patients platelet survival was only slightly shortened on the first day of therapy, but the decrease of the leucocyte count was also less in these patients. Diffuse intravascular coagulation, circulating immune complexes and complement activation were excluded as major causes of the shortened platelet survival. Although ALG reacted with platelets in vitro and in vivo (as detected with indirect immunofluorescence), bystander destruction was likely during the first ALG infusion when massive leucocyte destruction occurred.

Adolescent↗