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J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 91 records · Page 5Linked to original sources
PubMed1986

Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies.

Peripheral blood and bone marrow mononuclear cells from patients with refractory anemia (RA) or RA with sideroblasts (defined according to the revised French-American-British classification with less than 5% blast cells in the bone marrow) were analyzed using a panel of monoclonal antibodies directed against leukocyte antigens on B lymphocytes, T lymphocytes, monocytes, and myeloid cells. In the peripheral blood an increased proportion of T lymphocytes (and correspondingly a decreased proportion of B cells) could be demonstrated. However, when expressed in terms of absolute numbers, the T cell component was depressed because of severely decreased numbers of T4+ helper cells. In contrast, the absolute numbers of T8+ suppressor cells were either normal or increased in the majority of the patients. This resulted in markedly decreased ratios of T4+/T8+ cells, which were closely correlated to the number of transfusions given to the patients because of their refractory anemia. Finally, nearly all of the patients exhibited decreased numbers of cells reactive with the N901 natural killer (NK) antibody, thus explaining our earlier finding of decreased NK activity in these patients. In the bone marrow increased proportions of myeloid cells reactive with monoclonal antibodies present on immature myeloid cells (My7 and My9) were found, suggesting the presence of malignant clones. Indeed, when the numbers of My7+ cells and the morphologic evaluations of bone marrow smears at the time of diagnosis were compared to the progression of the disease, a group of patients with high numbers of My7+ cells and normal morphology could be identified that had a high probability of progression to refractory anemia with an excess of blasts or to overt acute myeloid leukemia. Thus, the use of antibodies defining leukocyte differentiation antigens might be of significant value in the diagnosis and prognostication of the myelodysplastic syndromes. These findings are discussed in relation to the pathogenesis of this potentially premalignant condition with special emphasis on possible defects in the immunologic defense mechanisms against early neoplasias.

Anemia, Refractory↗
PubMed1985

Immunomodulation of NK and ADCC by Corynebacterium parvum in acute myeloid leukaemia patients.

Natural killer (NK)- and antibody dependent cellular cytotoxicity assays were performed using cryopreserved effector cells in AML patients receiving i.c. and s.c. injections of Corynebacterium parvum. A dose related increase in NK could be demonstrated with peaks in NK at day 1 with full Cp dosage and at day 14 with 50% doses. This increase was attributable to the Cp vaccine since normal donors receiving tetanus toxoid or pneumococcal polysaccharide and AML patients randomized not to receive Cp did not show similar NK boosting. The increase was probably due to interferon induction in vivo and could be demonstrated with purified T- and non-T-lymphocyte subsets. However, longitudinal measurements showed that the ability of Cp to boost NK was gradually lost over 4-6 months. ADCC studies showed that while lymphocyte-ADCC was not consistently affected by Cp, monocyte-ADCC was enhanced with maximal cytotoxicity at day 14.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Further evidence for the B-cell nature of hairy cells. A study using immunostaining of splenic tissue with a wide panel of monoclonal antibodies.

Phenotypic characterization of neoplastic cells from 5 patients with hairy cell leukemia (HCL) was performed with 29 monoclonal and 6 polyclonal (anti-Ig) antibodies using immunoperoxidase staining of fresh frozen splenic tissue. Monotypic Ig was expressed in 4 cases, one case was non-expressive. Strong staining was obtained in all cases by monoclonal antibodies (MAs) specific for 3 pan-B-lymphocyte antigens (by anti-B 1, To 15, anti-Leu 12). Five other B-cell related antigens detectable with appropriate MAs (BA-1, anti-B2, DAKO-C3 b R, Tü 1, 38.13) were absent in all cases. The stainings with 13 T-cell associated MAs (OKT 3, OKT 4, anti-Leu 3 a, OKT 6, OKT 8, Tü 68, OKT 10, anti-Lyt 2, Tü 71, OKT 11, anti-Lyt 3, Tü 14, Tü 33) were all negative. Stainings with 4 MAs recognizing myelocytic and/or monocytic antigens (OKM 1, anti-Mo 1, anti-Mo 2, 3 C4) were also negative. We included 14 frozen biopsies with B-type chronic lymphatic leukemia (B-CLL) into our immunohistological study in order to establish phenotypic differences between HCL and B-CLL. Five MAs (Tü 1, anti-Lyt 2, Tü 71, BA-1 and anti-B2) gave consistently negative staining in HCL cases but positive staining in most or all B-CLL cases. The study provides significant evidence for the B-cell nature of HCL and also establishes important phenotypic differences between HCL and B-CLL.

Adult↗
PubMed1984

Natural killer (NK)-cell activity and antibody-dependent cellular cytotoxicity (ADCC) in primary preleukemic syndrome.

In 13 patients with a multi-parameter based diagnosis of primary acquired preleukemic syndrome (PPS), natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity (ADCC) were investigated on peripheral blood mononuclear cell (MNC) fractions. In all but two patients a defective NK activity was found. Lymphocyte-monocyte mixture experiments demonstrated that this was not due to suppressor monocytes. Furthermore, NK activity was defective when both myeloid and non-myeloid target cell lines were used. Addition of human leukocyte interferon to the NK cultures augmented the cytotoxicity, which exhibited the same kinetics as that of normal controls, but NK activity levels remained subnormal. These data strongly indicate that the decreased NK activity seen in the patients is due to a decreased number of circulating NK cells. In contrast ADCC was within the normal range both when MNC suspensions as well as when purified peripheral blood lymphocytes were used as effector cells thus ruling out subnormal lymphocyte ADCC masked by the presence of monocyte ADCC. These results demonstrate that PPS patients have a selective NK defect with an intact lymphocyte ADCC function. Whether this defect will prove to be valuable in the assessment of a malignant transformation in a given patient will await further longitudinal NK studies and clinical follow-up of the patients.

Adult↗
PubMed1984

Breast tumour as a first manifestation of extramedullary relapse in acute lymphoblastic leukaemia.

After 2 years of maintained complete remission, a 17-year old girl suffering from common acute lymphoblastic leukaemia (C-ALL) developed a mass in the right breast. Determination of the tumour cell phenotype using a panel of monoclonal antibodies demonstrated the presence of leukaemic blasts. At this stage no other sign of relapse could be demonstrated. Later, however, when the leukaemia progressed despite aggressive treatment, blasts with the same surface phenotype as the ones in the breast were obtained both from repeated biopsies from a mediastinal mass and from a lower abdominal mass. Manifestation of first relapse in ALL presenting as a breast tumour has never been described before and may be added to other unusual extramedullary sites of relapse. The significance of immunologically defined phenotyping of cells from tissue biopsies is underlined.

Adolescent↗
PubMed1984

Aclarubicin in the treatment of acute nonlymphocytic leukemia refractory to treatment with daunorubicin and cytarabine: a phase II trial.

Aclarubicin (ACR) was administered in a prospective cooperative phase II trial to 44 patients with possibly refractory acute nonlymphocytic leukemia who were previously treated with daunorubicin and cytarabine. Induction treatment consisted of 80 mg/m2 of ACR iv daily for 3 days, followed by 80 mg/m2 iv daily for 2 days in patients not obtaining a complete remission (CR) after 2-4 weeks. CR was observed in eight patients (18%) and partial remission was observed in six (14%). On monthly maintenance chemotherapy with ACR and cytarabine, the duration of CRs varied between 10 and 58 weeks. Achievement of remission was not related to age, presence or absence of Auer bodies, cytogenetic characteristics, or previous response to daunorubicin and cytarabine. Side effects were nausea and vomiting observed in 86% and diarrhea in 34% of the patients, whereas mucositis and alopecia were uncommon. Disturbances of cardiac function arousing suspicion of acute ACR toxicity were observed in seven patients. No case of chronic cardiotoxicity was observed, despite the fact that 20 patients received ACR doses greater than 400 mg/m2, with seven of the 20 having had a previous daunorubicin dose greater than 400 mg/m2. As CR was obtained in four of 14 patients with primary therapy-resistant leukemia and in two of 16 patients with relapse and no response to re-treatment with daunorubicin and cytarabine, ACR does not seem to show clinical cross-resistance to daunorubicin. Evaluation of ACR in first-line chemotherapy of acute nonlymphocytic leukemia appears justified.

Aclarubicin↗
PubMed1983

Adjuvant immune stimulation with Corynebacterium parvum during maintenance chemotherapy of acute myeloid leukemia. A prospective randomized study.

Of 93 consecutively treated patients with acute myeloid leukemia 36 (39%) achieved complete remission (CR). Thirty-five patients were randomized to receive either maintenance chemotherapy alone (C) or a combination of active nonspecific immunotherapy with Corynebacterium parvum and chemotherapy (C + I). Maintenance therapy was given monthly for 1 year or until relapse. The median survival time was 21 months for patients treated with chemotherapy alone, compared with 30 months for patients treated with chemotherapy and immunotherapy. The median remission duration was 15 months for patients treated with chemotherapy, compared with 18 months for chemotherapy and immunotherapy group. While no statistically significant difference in remission duration or survival time could be attributed to the use of immune stimulation, a plateau of 40% long-term time survivors was defined in the chemotherapy and immunotherapy group. Age and sex were found to be the major prognostic factors for achievement of CR. No difference was found in remission duration or survival between the two different induction schedules. Neither did the morphological subtype of AML (FAB classification) or the leukocyte count at diagnosis correlate with remission rate or survival.

Adjuvants, Immunologic↗
PubMed1983

Complement studies in splenectomized patients.

Total haemolytic complement activity, C2, C5, total alternative pathway activity, factor B, and C3d were measured in 85 splenectomized patients from 1 month to 32 years after splenectomy. Furthermore the patients were investigated for circulating immune complexes. No major deficiencies of the complement factors were detected. In a few patients a reduced C2 level was caused by genetically determined defects or was due to complement consumption in conjunction with circulating immune complexes. The complement levels were normal in 2 patients who had survived overwhelming infections after splenectomy. C5 was elevated in a major proportion of the patients, and it is suggested that this might be caused by post-splenectomy monocytosis. Circulating immune complexes were found in 20% of all cases, irrespective of the presence of residual splenic tissue. Thus the commonly cited impairment of the complement system after splenectomy does not seem to be substantiated, and the deficient resistance against bacterial infections in splenectomized patients does not seem to include abnormalities of the complement system.

Adolescent↗
PubMed1983

The cellular immune response after splenectomy in humans. Impaired immunoglobulin synthesis in vitro.

The in vitro immune functions of peripheral blood lymphocytes have been studied in 70 splenectomized patients. 45 patients were splenectomized due to traumatic rupture of the spleen; in 22 of these patients residual splenic tissue was detected, employing a selective spleen scintigraphy. 14 patients were splenectomized due to hereditary spherocytosis and 11 patients due to immune thrombocytopenia or autoimmune haemolytic anaemia; they were all without ectopic splenic tissue. The study revealed that splenectomized patients have (i) an elevated number of blood lymphocytes, (ii) an elevated relative number of EA-RFC, but normal %s of E, EAC-RFC and SmIg positive cells, (iii) normal T-cell mitogenic responses induced by PHA, but enhanced responses induced by ConA and PWM, (iv) normal cell-mediated enhancement of the PWM-induced proliferative B-cell response, (v) no cell-mediated inhibition of the T-cell dependent and PWM-induced proliferative B-cell response and (vi) an impaired number of PFC after stimulation with PWM. The findings were unrelated to the cause of the splenectomies or to the presence of residual splenic tissue. It is possible that the impaired B-cell response as shown by the reduced number of PFC after stimulation with PWM may be of significance for the in vivo resistance to infections in splenectomized patients.

B-Lymphocytes↗
PubMed1983

Immunoglobulin classes and persistence of anti-pneumococcal antibodies in splenectomized adults and adolescents after pneumococcal vaccination.

The IgG-, IgM- and IgA- anti-pneumococcal antibody response to pneumococcal vaccination in 29 splenectomized adults and adolescents with hereditary spherocytosis or previous traumatic splenic rupture was determined by an enzyme-linked immunosorbent assay. It was not significantly different from that of 12 healthy controls except for a lower IgM class antibody increase in the splenectomized against one of four antigens studied. The antibody response was predominantly of IgG class, but significant increases in IgM and IgA class antibodies against all four antigens (polysaccharide types 2, 6A, 12F and 14) studied were observed. In 1/29 splenectomized and 2/12 healthy individuals (7%) the IgG antibody class did not predominate. In 36 adults and adolescents splenectomized due to traumatic rupture or during surgery for gastric ulcer, 77% of the peak geometric mean total antibody concentration four weeks after vaccination was still present after 21 months (16-26 months).

Adolescent↗
PubMed1983

Stimulation of monocyte-mediated, antibody-dependent cytotoxicity in mycosis fungoides.

Antibody-dependent cytotoxicity mediated by purified blood monocytes were determined in untreated patients with plaque-stage mycosis fungoides (MF), parapsoriasis en plaques, exfoliating erythroderma, and noncutaneous malignant lymphoma. Compared with healthy control subjects and control subjects with varicose ulcers, patients with MF had increased monocyte cytotoxicity. In the other dermatoses, normal monocyte cytotoxicity was found. Patients with noncutaneous malignant lymphoma showed normal or decreased monocyte cytotoxicity. There was no evidence that abnormal monocyte cytotoxicity in cutaneous and noncutaneous malignant lymphoma were caused by interaction with lymphocytes or serum. The presence of increased monocyte cytotoxicity in patients with plaque-stage MF may be a clinically useful finding when this diagnosis is suspected clinically but not proved histopathologically.

Adult↗
PubMed1982

Influence of residual splenic tissue on autoantibodies in splenectomized patients.

In 42 patients splenectomized after injury of the spleen or for non-malignant diseases residual splenic tissue was detected by 99mTc scanning in 19 (Group I) and not detected in 23 (Group II). Autoantibodies detected by the indirect immunofluorescent method occurred in 16 (38%) of the splenectomized patients and in 6 (14%) of 42 age- and sex-matched controls (P less than 0.02). In patients with residual splenic tissue the incidence of autoantibodies did not differ significantly form that in the controls, whereas autoantibodies occurred significantly more often in patients without residual splenic tissue (39%) than inthe corresponding control groups (9%) (P = 0.016). Antibodies to nuclear antigens (ANA), smooth muscle (SMA), reticulin (RetA) and cytoplasm of gastric parietal cells (PA) were detected, and the antibody titres tended to be higher in the patients than in the controls. None of the patients showed any clinical signs of autoimmune disease. These findings indicate that splenectomy disturbs the regulation of autoantibody function, and it is possible that this might be caused by a reduction of the number of T suppressor cells for which the spleen is a major pool. It is suggested that residual tissue may prevent an increased occurrence of autoantibodies in splenectomized patients.

Adolescent↗
PubMed1982

Free light chains of immunoglobulins in serum from patients with leukaemias and multiple myeloma.

The serum concentration of free kappa and lambda light chains of immunoglobulins were measured in 114 patients with myelo- and lymphoproliferative disorders including multiple myeloma. Increased concentrations of a single light chain type, suggesting monoclonal origin, were found with high frequency in B-cell diseases only. Thus 6 out of 9 patients with chronic lymphatic leukaemia and 24 of 28 patients with multiple myeloma had increased concentrations of a single chain type. The highest values reported in chronic lymphatic leukaemia were approximately 10 and in multiple myeloma 1000 times normal mean. Cytostatic treatment of chronic lymphatic leukaemia was followed by a decrease in the light chain levels. The levels were, however, not correlated to the number of circulating lymphocytes, the lymphatic infiltration of tissue or clinical activity. Increased concentrations of both chain types, suggesting a polyclonal origin, were found in both of 2 patients with acute monocytic leukaemia, 6 of 7 with acute myelomonocytic leukaemia, 2 of 23 with acute myeloid leukaemia and 1 of 7 with acute lymphoblastic leukaemia. The highest levels of light chains in these groups were 5 times normal mean. All patients with myeloproliferative disorders revealed normal values of both light chain types.

Adolescent↗
PubMed1982

Failure of pneumococcal vaccination in a splenectomized child.

Recurrent Streptococcus pneumoniae septicaemia occurred in a splenectomized child with idiopathic thrombocytopenic purpura. Fatal infection took place 1 year after pneumococcal vaccination and was caused by sero-type 18C which was included in the vaccine. The efficacy of pneumococcal vaccination is discussed in relation to specific pneumococcal polysaccharide antibody titers, and it is concluded that vaccination alone is insufficient in preventing overwhelming infections in splenectomized individuals.

Antibodies, Bacterial↗
PubMed1982

Antibody response to pneumococcal vaccine in splenectomized adults and adolescents.

The antibody response of 67 splenectomized adults and adolescents with benign underlying diseases to a 14-valent pneumococcal capsular polysaccharide vaccine was determined by an enzyme-linked immunosorbent assay. It was not significantly different from that of 12 healthy non-splenectomized adult volunteers for 13 of the 14 polysaccharide antigens studied. Residual splenic tissue as detected by Tc-scintigraphy was without any influence on the vaccination response. In comparison 5 untreated splenectomized adults with malignant diseases and 11 splenectomized adults receiving immunosuppressive therapy exhibited a significantly reduced combined geometric mean of their postvaccination antibody concentrations (all 14 antigens added) and of their combined geometric mean antibody fold increase as compared to the healthy non-splenectomized adults. The reduction in antibody response was most pronounced in the group of immunosuppressed patients. Immunogenicity of each of the 14 vaccine antigens varied considerably as judged by the geometric means of the postvaccination arbitrary antibody concentrations. Also individual variation in postvaccination antibody concentration against each antigen was large.

Adolescent↗