Search PubMed⌕ Search

Biomedical subjects

J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 55 records · Page 3Linked to original sources

Induced and down-regulated proteins in the human cultured hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi during incubation with interferon-alpha: a kinetic study.

To elucidate the mechanism of action of interferon-alpha (IFN-alpha), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-alpha incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed that the changes in JOK-1 cells were only temporary (within 8-16 h) and small to moderate in magnitude (less than four-fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30-fold). Quantitative analytical assessments indicated that four IFN-alpha-inducible polypeptides, present in low amounts of untreated cells, were highly expressed only in sensitive Daudi cells upon IFN-alpha treatment. This observation might indicate a role for these polypeptides in the inhibition of cell proliferation in Daudi cells. Furthermore, six of the other IFN-alpha-modulated polypeptides were synthesized constitutively in JOK-1 cells at levels comparable to those achieved in IFN-alpha-treated Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Burkitt Lymphoma↗

Gingival status during chemical plaque control with or without prior mechanical plaque removal in patients with acute myeloid leukaemia.

The purpose of the study was to evaluate the effect of a mouthrinse regimen comprising both chemical plaque control and mechanical plaque removal. 20 adult patients with acute myeloid leukaemia were assigned to one of the following 2 regimens: (1) (group 1) mouthrinse twice daily with a 0.1% chlorhexidine solution; or (2) (group 2) the same regimen, but preceded by mechanical removal of plaque and calculus on day 1. All patients were followed for 28 days from the initiation of remission-induction therapy. In group 2, the plaque scores remained lower than those of group 1 throughout the study, although only 3 patients remained completely free of plaque after 28 days. Gingival inflammation as judged by bleeding scores remained unchanged in group 1, whereas in group 2, the degree of inflammation was reduced from 52% (median value) on day 1 to 31% (median value) on day 28. The bleeding scores were also lower in group 2 (31%) than in group 1 (60%) on day 28. No differences were found between the 2 groups with respect to the occurrence of other oral infections. It is concluded that chemical plaque control with chlorhexidine should be preceded by mechanical removal of plaque and calculus, when used in patients with acute myeloid leukaemia and thrombocytopenia.

Aclarubicin↗

Hybrid acute leukemia: therapeutical implications of immunological phenotyping.

We phenotyped blood and bone marrow cells from a patient with acute Ph1+ acute leukemia longitudinally during the four months he received intensive chemotherapy. At presentation this case of biphenotypic acute leukemia had two immunologically different types of blast cells, one expressed CD10 (CALLA), CD13 (MY7) and CD33 (MY9) but lacked CD20 (B1), the other type expressed no CD10 or CD33. The phenotype, during AML induction therapy, changed to a more CD10+, CD20+ ALL one. ALL therapy based on these findings induced improvement in bone marrow function but the patient died of septicemia at day 134. The use of concomitant immunophenotyping (IP) and cell cycle analysis had shown proliferation advantage of the more lymphoid malignant cells. These results suggest that it is possible to induce lineage-associated changes in the phenotype of hybrid malignant cells and that these leukemias might be treated best according to longitudinal immunophenotyping of the blast cells.

Adult↗

Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of poor prognosis.

In a series of 100 acute myeloid leukemia (AML) patients defined by cytochemistry and immunophenotyping, 20 expressed T-lymphocyte associated antigens on the surface of their blasts. While 15 expressed two or more T-cell antigens, five were found to express only CD7. All patients belonged to the French-American-British type M4, and four were under the age of 40. Despite intensive chemotherapy, four never obtained a complete remission and the fifth died of relapse after an allogenic bone marrow transplantation. While 12 randomly selected T-cell antigen negative AML patients showed only few rearrangements in Ig- or T-cell receptor (TCR) genes, such genetic alterations were demonstrated in four of five patients for the TCR delta gene and in all patients for the TCR beta gene. Interestingly, DNA fragments of similar size were demonstrated in three of five patients for both the beta and delta genes. These data suggest that the solitary presence of CD7 among T-cell antigens in otherwise clearcut AML cases identifies a group of patients with similarities in antigen receptor gene configuration as well as outcome.

Acute Disease↗

[Autologous bone marrow transplantation in malignant blood diseases].

The authors present the organisation and preliminary experience with a comprehensive autologous bone marrow transplantation (ABMT) program in patients with malignant blood diseases. The procedure involves harvesting of bone marrow from patients in complete remission, purification of mononuclear cells and cryopreservation of these at -196 degrees C. After bone marrow cultures show that a sufficient number of hemopoietic progenitor cells (CFU-GM) are present in the marrow to reconstitute the patient, he/she is conditioned with chemo- (busulphan/cyclophosphamide (Bu + Cy)) or chemo/radiotherapy (total body radiation/cyclophosphamide (TBI + Cy)) in doses equal to those commonly used in allogeneic BMT. From February 1988 to July 1990 bone marrow (BM) was harvested from 24 patients. The median yield of mononuclear cells (MNC) was 1.2 x 10(8)/kg body weight (range 0.55-3.7). After buffy coat preparation, density gradient centrifugation, cryopreservation and thawing out, 0.60 x 10(8) MNC/kg (0.18-3.3) corresponding to 9.3 x 10(4) CFU-GM/kg (2.28-144) could be recovered. Twelve patients have received transplants, five with AML (after Bu + Cy conditioning), six with lymphoblastic lymphoma and one with Hodgkin's disease (with TBI + Cy conditioning). The median number of days to obtain greater than 1.0 x 10(9) leucocytes/l, greater than 0.5 x 10(9) neutrophils/l, greater than 50 x 10(9) thrombocytes/l and last requirement for erythrocyte transfusion were 21 (12-49), 28 (10-60), 55 (21-270) and 55 (12-129) days, respectively. Four patients had sepsis and the median duration of hospitalization was 39 (22-58) days. The most severe complications were seen in the AML patients, two of whom died during the posttransplant period (one of septicemia, one of thrombocytopenic bleeding).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study. The Nordic Myeloma Study Group (NMSG)

In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.

Adult↗

Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

Aclarubicin↗

Herpes simplex virus and intraoral ulcers in immunocompromised patients with haematologic malignancies.

Possible factors predisposing to the development of intraoral ulcers in immunocompromised patients with haematologic malignancies were investigated. Among 46 patients undergoing antineoplastic treatment, 18 developed an intraoral ulcer during the prospective study. Patients with or without ulcers were comparable with respect to underlying disease, presence of teeth, the qualitative composition of the aerobic and facultatively anaerobic oral microflora, herpes simplex virus (HSV) titer positivity, a past history of herpes labialis, leukocyte and thrombocyte counts, and duration of fever. Viral cultures from saliva revealed an association between the presence of HSV in saliva and the presence of intraoral ulcers. HSV was not isolated from the saliva of any patient without ulcers. Viral cultures from the ulcers revealed growth of HSV in 11 (61%) of the 18 patients with ulcers. HSV-positive ulcers were located more often on the alveolar process than elsewhere in the oral cavity. Ulcers on the lateral borders of the tongue and on the buccal mucosa were found only in dentate patients. Development of intraoral ulcers was not associated with an increase of the HSV titer in serum in any patient. It is concluded that some intraoral ulcers, especially when located on the alveolar process, are associated with and probably caused by HSV, while mechanical trauma during mastication seems likely to be involved in the pathogenesis of ulcers elsewhere in the oral cavity.

Adult↗

Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview.

The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune system becoming very effective. Even though no major changes in the composition of the major mononuclear leukocyte subsets could be demonstrated a significant increase in natural killer function was demonstrated. These data suggest that relaxation and guided imagery might have a beneficial effect on the immune defense and could form the basis of further studies on psychological intervention and immunological status.

Adult↗

[Accumulated microbiological data. Surveillance of infection/antibiotic policy].

Database reviews of the findings in bacteriological specimens from a period of six years from patients in a department of haematology are employed as a model of how cumulative data about the microorganisms isolated may be employed for surveillance of accumulated infections and in the organization of the antibiotic policy of a department. During the period of observation, the standard treatment with antibiotics for febrile episodes in granulocytopenic patients was altered to piperacillin and netilimicin on the basis of the frequent occurrence of Gram-negative rods including Pseudomonas aeruginosa in blood cultures. It is concluded that accumulated microbiological data is of value for a clinical department and that analysis of the data does not constitute an increased work-load provided that the microbiological reports are routinely registered in a database.

Anti-Bacterial Agents↗

[Myelomatosis. A study of 138 patients treated with melphalan, prednisone and vincristine with particular attention to the prognostic value of a stage subdivision].

With the object of evaluating three recognized prognostic stage subdivision systems for myelomatosis, retrospective data from 138 patients treated from 1976 to 1986 were employed. During this period, uniform therapeutic principles were employed, viz interval treatment with melphalan and prednisone supplemented, in cases of anaemia or raised serum creatinine, with vincristine. The prognostic significance for survival was calculated from variables at the time of diagnosis. The major prognostic factors were: age, tumour cell mass assessed by plasma cell percentage in the bone-marrow aspirate and/or M-component concentration, demonstration of Bence-Jones protein, renal function and the haemoglobin and calcium concentrations in the blood. Stage subdivision according the principles established by the Medical Research Council based on haemoglobin concentration and renal function were the best for assessing the prognosis in treated patients. Autopsy was performed on 55 out of the 96 patients who had died. The commonest cause of death was infection (75%).

Aged↗

Whole blood assay for NK activity in splenectomized and non-splenectomized hairy cell leukemia patients during IFN-alpha-2b treatment.

Natural killer cell (NK) activity in peripheral blood (PB) was followed longitudinally for up to 2 yr after initiation of low-dose IFN-alpha-2b therapy in nine hairy cell leukemia (HCL) patients. A whole blood NK (WB-NK) assay was employed in order to measure the NK activity per unit blood. The pretreatment WB-NK activity was consistently low, indicating that the patients' total NK activity in PB is decreased. Striking differences in WB-NK activity were observed between splenectomized and non-splenectomized patients, whereas no consistent patterns were found when using the conventional NK assay. Thus the WB-NK activity of splenectomized patients showed an immediate increase after initiation of treatment, while the activity in non-splenectomized patients decreased and remained low during the first 3-6 months. Subsequently, after reduction in spleen size, the WB-NK activity began to increase. In splenectomized patients, a second rise in WB-NK was observed after 3-6 months of therapy, coinciding with the normalisation of the peripheral blood counts. In both groups of patients incubation with IFN in vitro induced a rise in NK activity before start of treatment, which was abrogated promptly after initiation of therapy, indicating a maximal in vivo boosting of the NK cells. These differences observed indicate that the response of splenectomized and non-splenectomized HCL patients to IFN treatment should be evaluated separately.

Cytotoxicity, Immunologic↗

Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5'-oligoadenylate synthetase activity.

A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression of several antigens positive for T cells, B cells, NK cells and monocytes, the use of a double marker specific for hairy cells was needed to distinguish the different subpopulations. Analysis of LDA in peripheral blood (PB) showed a total normalization of the T cell and monocyte numbers within 90 days, the number of NK cells normalized in 90 to 180 d, whereas normalization of B cell number was seen only after 180 to 360 d of treatment. Mean pretreatment 2-5A synthetase activity was normal or low, but upon treatment the levels rose immediately to higher than normal values and remained high throughout the study. Pretreatment NK activity was low, but normalized after between 90 to 360 d, except in 2 patients with severe splenomegaly. In vitro incubation of peripheral blood mononuclear cells (PBMNC) with IFN-alpha induced activation of the NK and 2-5A synthetase activity in untreated patients, but with treatment these effects were gradually abolished, indicating an increasing effect of IFN-alpha in vivo with time. These results shows that the different PBMNC subpopulations and important immunological functions normalize with treatment. This normalization is, however, not seen until at least after 1 year of treatment, indicating that the treatment schedule should be longer. As no exhaustion to the effect of IFN was seen, as measured by the 2-5A synthetase activity, a continuing beneficial effect of treatment is anticipated. The increasing effect of IFN-alpha after the first signs of clinical effect suggests that the doses used in the present study were higher than necessary.

2',5'-Oligoadenylate Synthetase↗

Preferential localisation of red cell vacuoles to pathologically shaped human red blood cells.

The percentage of pitted erythrocytes and Howell-Jolly bodies in peripheral blood samples of 51 individuals following posttraumatic splenectomy and 20 patients splenectomized because of various haematological diseases differed significantly from each other (p less than 0.001) and from that of healthy controls (p less than 0.001). The percentage of pitted erythrocytes was significantly higher in pathologically shaped red blood cells (RBCs) (acanthocytes, schizocytes, elliptocytes) than in normal discoid shaped RBCs (p less than 0.001). As the number of pits per RBC showed great individual variations, a scoring system for the evaluation of pitted RBCs is proposed.

Adult↗

Effect of plaque removal on patients with acute leukemia.

The aim of the present investigation was to study the effect of daily plaque removal on gingival inflammation and the occurrence of oral mucosal ulcers in granulocytopenic patients with acute myeloid leukemia. Eleven patients were analyzed prospectively and consecutively during a period of 28 days, in which the patients were treated with antineoplastic drugs. The patients had their teeth scaled, and plaque was removed daily. On Day 1 all had gingival inflammation, and two had profound periodontitis with pocket depths and loss of attachment greater than 5 mm. During the treatment period plaque scores were reduced in all patients and a corresponding decrease in gingival inflammation was seen. It was possible to obtain healthy gingiva during treatment with cytotoxic drugs. In addition, the development of oral mucosal lesions was low compared with other studies. This study demonstrates that daily plaque removal from the teeth resolves gingival inflammation also in severely granulocytopenic patients.

Adult↗

Potentially pathogenic microorganisms in the oral cavity during febrile episodes in immunocompromised patients with haematologic malignancies.

The purpose of the study was to describe the occurrence of potentially pathogenic microorganisms during febrile episodes in haematologic patients, who had been treated with anti-neoplastic drugs within the previous 4 weeks. During a 9-month period 78 consecutive febrile episodes occurred in 46 patients who were examined daily. On day 1, before antibiotic treatment was started, members of the normal flora were found in 83%, Candida spp. in 72%, Enterobacteriaceae in 29%, Pseudomonas aeruginosa in 8%, Staphylococcus aureus in 14%, coagulase-negative staphylococci in 26% and enterococci in 17% of the febrile episodes. During the subsequent antibiotic treatment, the prevalence of members of the normal oral flora was markedly reduced from day 1 (83%) to day 7 (6%), and the normal flora was replaced by potentially pathogenic microorganisms. A rise was found in the prevalences of Candida spp. (from 72 to 92%) and coagulase-negative staphylococci (from 26 to 49%) from day 1 to day 4. The prevalences of Enterobacteriaceae and P. aeruginosa showed no day-to-day changes, and were not different in patients hospitalized for more or less than 24 h prior to inclusion into the study, suggesting that their detection was not due to acquisition during hospitalization or antibiotic treatment. The oral occurrence of species of microorganisms regularly found in septicaemia, suggests that the oral cavity may play a role as a port of entry of septicaemia in patients with haematologic malignancies.

Adult↗

Immunoelectron microscopy studies on the modulation of common acute lymphoblastic leukemia antigen (CALLA) on NALM-6 cells: delineation of intracellular transport.

Even though much is known about the presence of the common acute lymphoblastic leukemia antigen (CALLA) with respect to its distribution in hematopoietic and non-hematopoietic tissues, its functional role in lymphoid cells is as yet unknown. Given the fact that CALLA is completely modulated on the surface of lymphoid cells, we have employed pre-embedding immunogold techniques at electron-microscopical level and demonstrated that J5 monoclonal antibody (MoAb)-mediated modulation of CALLA expression on the lymphoblastic cell line NALM-6 is a specific, rapid process, closely resembling receptor-mediated endocytosis. Furthermore, it was found that CALLA was internalized through plasmalemmal pits and cytoplasmic vesicles and processed intracellularly in multivesicular bodies and secondary lysosomes. In contrast, HLA-DR antigen remained at the cell surface upon contact with specific MoAb. These data suggest that CALLA might be a receptor for a hitherto unknown signal molecule.

Antigens, Differentiation↗