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Biomedical subjects

J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 109 records · Page 6Linked to original sources

Serum angiotensin-converting enzyme and blood monocytes in splenectomized individuals.

In 45 splenectomized individuals without malignancies, residual splenic tissue was detected by 99mTc-scanning using reinjection of labelled heat-damaged and autologous erythrocytes. The angiotensin-converting enzyme in serum (SACE) and the blood monocyte count were measured in order to demonstrate an eventual association between these parameters as well as the influence of residual splenic tissue. In 20 patients with detectable spleen tissue SACE was normal (26.2 +/- 4.4 U/ml), but in 25 patients without residual spleen tissue SACE was slightly elevated (28.7 +/- 6.4 U/ml; p less than 0.02) as compared with healthy controls (24.4 +/- 6.2 U/ml). In both groups of patients blood monocytes were markedly increased. However, no correlation could be demonstrated between SACE and the monocyte count in any group. In 2 patients SACE was above the upper limit of the normal range (greater than 36.8 U/ml) as found in sarcoidosis but no signs of this disease could be demonstrated. It is concluded that splenectomy must be taken into account when the significance of raised SACE is evaluated. It may be suggested that the spleen exerts an effect on the metabolism of SACE or on the ACE-producing cells in the organism.

Adolescent↗

Detection of splenosis and ectopic spleens with 99mTc-labelled heat damaged autologous erythrocytes in 90 splenectomized patients.

Splenosis or ectopic spleens were detected in 22 of 45 patients splenectomized after either abdominal trauma or accidental lesions of the spleen during operation. The incidence of ectopic spleen tissue in various groups of splenectomized patients has been investigated by a sensitive scanning method employing reinjection of 99mTc-labelled heat damaged autologous erythrocytes. In comparison 7 cases were found among 45 patients who underwent splenectomy for haematological reasons. The time span between the operation and a positive scan varied between 3 months and 11 years. None of the patients in the haematological group with reoccurrence of spleen tissue presented any signs of relapse of their primary disorder. The only patient with overwhelming infection was a girl in whom splenectomy was performed for hereditary spherocytosis. She recovered from the sepsis and her scan was negative. It is concluded that recurrence of spleen tissue is frequent after traumatic lesions of the spleen but rare after selective splenectomy for haematological reasons. This may account for the lesser tendency to overwhelming sepsis after post-traumatic splenectomy.

Adolescent↗

Subclassification in acute lymphoblastic leukaemia: acid phosphatase reaction and immunological markers in relation to clinical features. A comparative study of 44 patients.

A prospective, comparative study of cytochemical and immunological markers and clinical features was undertaken in 44 patients with ALL (children and adults). 12 patients (27%) had T-ALL, 1 patient (2%) B-ALL and 31 patients (71%) (non-T, non-B)-All. E-rosetting lymphoblasts ranged from 35 to 96% (median: 61), highest when AET-treated SRBC were used as indicator cells. All 12 E-rosette positive cases were strongly acid phosphatase (AcP)-positive, showing a homogeneous pattern of distinct granular AcP-activity in more than 85% of the lymphoblasts (median: 96%) significantly different from the median of 26% granulated blasts found in (non-T, non-B)-ALL cases. Counting blasts with granular AcP-activity proved to be both easier than using a scoring system for the AcP-reaction and more efficient in terms of discriminating ability between the subgroups. Significant clinical and haematological features characterizing the T- and AcP-positive cases included: (1) Predominance of young adult men, (2) presence of a mediastinal mass, (3) involvement of skin and serous membranes, (4) only slightly affected haemoglobin concentration at presentation, (5) difficulty in obtaining complete remission, (6) shorter duration of first complete remission and (7) shorter survival rate. It is confirmed that AcP-staining of lymphoblasts is an easy, reproducible and inexpensive method for identifying the T-cell variety of ALL.

Acid Phosphatase↗

Monocyte cytotoxicity after splenectomy.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by monocytes was determined in 45 adults approximately 4 years after splenectomy for either abdominal trauma or accidental injury during operation for benign gastroduodenal ulcer. Compared to controls, both groups of splenectomized persons showed increased numbers of monocytes and decreased monocyte ADCC. The decrease of monocyte ADCC was only significant in those splenectomized persons in whom accessory splenic tissue was not detectable by isotope scanning. Addition of the spleen-dependent peptide tuftsin to monocytes in vitro did not augment their ADCC. An increase serum concentration of immune complexes was neither related to the presence of splenic tissue nor to the monocyte cytotoxicity. Vaccination with pneumococcal polysaccharide had no effect on monocyte ADCC. It is suggested that the defective monocyte cytotoxicity observed in splenectomized persons without detectable splenic tissue might be relevant to post splenectomy infectious susceptibility.

Adult↗

Monocyte-mediated antibody-dependent cytotoxicity. Modulation by Glycolysis and insulin.

In suspensions of purified human monocytes from 14 healthy persons the antibody-dependent cell-mediated cytotoxicity (ADCC), the lactate release, and the glucose uptake were studied. In non-stimulated monocytes ADCC correlated with lactate release and glucose uptake. Following addition of insulin a dose-related rise in ADCC, lactate release, and glucose uptake was observed. For each of the three processes the maximal insulin effect was about 30%. Most of the stimulation was seen within the physiological concentration range of insulin, and the insulin concentration resulting in 50% of the maximal effect was nearly the same for ADCC, lactate release, and glucose uptake (about 100 pM). The insulin stimulation of ADCC correlated with the stimulation of lactate release and glucose uptake. An inverse correlation between the ADCC of non-stimulated monocytes and the insulin stimulation of ADCC was demonstrated. No relationship was found between monocyte maturity and any of the three variables of monocyte function, either with or without insulin. These results indicate that, for normal monocytes, the cytotoxic capacity is closely related to the glycolysis.

Adult↗

Human lymphocyte and mouse erythrocyte rosettes. Optimization of the assay.

Rosettes formed between lymphocytes and unsensitized mouse erythrocytes not only detect a subset of normal b-lymphocytes, but furthermore seem to be of considerable importance in the differential diagnosis of various B cell malignancies. From a series of experiments aimed at optimizing this rosette test, we conclude: (1) Erythrocytes from different mouse strains vary in their affinity for lymphocytes; (2) Experimental conditions are less strict when testing chronic lymphatic leukaemia lymphocytes than normal lymphocytes; (3) Treatment with the sulphydryl compound aminoethyl-isothiouronium bromide, which enhances sheep erythrocyte rosette formation, has an opposite effect on mouse rosettes, and (4) Neuraminidase treatment of the lymphocytes is not necessary when optimal experimental conditions are used.

Animals↗

Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays.

This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunologic techniques including detection of ALL antigens and terminal transferase. The malignant cells were subsequently found to be potent effectors in NK and ADCC assays. Addition of partially purified alpha-interferon to the in vitro cultures was found to have an enhancing effect on NK activity, whereas no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells.

Aged↗

Suppressor T-lymphocytes and auto-anti-B-cell cytotoxic T-lymphocytes in a case of acquired hypogammaglobulinaemia.

A case of acquired hypogammaglobulinaemia has been examined. Total and differential leucocyte counts and distribution were normal as were the lymphocyte sub-populations when defined by surface membrane immunoglobulin, E-, EA- and EAC-rosette techniques. The proliferative response of unseparated lymphocytes to PHA and Con-A was normal while the response to PWM was clearly impaired. In contrast, testing of purified B-lymphocytes by PWM was within the normal range. The response to PWM was found to be depressed by adding the patient's T-lymphocytes to autologous B-lymphocytes as well as to B-lymphocytes from 10 normal, healthy controls. The patient's T-lymphocytes were further tested for cytotoxicity against autologous. B-lymphocytes and B-lymphocytes from the 10 control individuals. Cytotoxicity was observed against autologous B-lymphocytes and against the B-lymphocytes of 3 controls. These findings indicate the presence of peripherally circulating unspecific T-suppressor lymphocytes and cytotoxic T-lymphocytes of some immunogenetic specificity. The suppressor and cytotoxic T-lymphocytes may separately or in combination be involved in the pathogenesis of hypogammaglobulinaemia. Thus, these findings are equivocal but underline the immunologic aspects of the pathogenesis.

Agammaglobulinemia↗

Serum beta 2-microglobulin in acute and chronic leukaemia.

The serum concentration of beta 2-microglobulin (beta 2-m) was measured in 69 patients with acute or chronic lympho- and myeloproliferative disorders. Serum beta 2-m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta 2-m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta 2-m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta 2-m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta 2-m. Also no significant changes in serum beta 2-m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta 2-m in patients with chronic leukaemia may reflect the total amount or turn-over of leukaemic cells in the body and that repeated determinations of serum beta 2-m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta 2-m seems to be of little, if any, clinical use in leukaemia.

Adolescent↗

Transfer factor in mycosis fungoides: three years experience.

13 patients with clinically and histologically verified mycosis fungoides were treated with transfer factor as additional therapy to the hitherto conventional treatment after this had failed. After approximately 3 years, complete remission was present in 3 patients, 4 patients were significantly improved and registered as being in partial remission, while the condition was registered as no change in 3 patients. 1 patient was found worse, 1 patient had died after discontinuation of therapy and 1 patient was out of the study. In this case treatment was withdrawn because of the development of contact urticaria to nitrogen mustard, her basic therapy. The number of T lymphocytes, which was low prior to treatment, increased to normal values during the therapeutic period. During the first year a decrease in serum IgE was noted. The results of the clinical evaluation seem to indicate that transfer factor may be of value as an additional therapeutic agent in mycosis fungoides. Controlled investigations are needed and are in progress.

Adolescent↗

Immunomodulation by Corynebacterium parvum in normal humans.

Four normal human donors were immunized with 2 mg of heat-killed Corynebacterium parvum by subcutaneous and intracutaneous injections, and lymphocyte surface markers, antibody-dependent (ADCC), and spontaneous cell-mediated (SCMC) cytotoxicities followed for a 28-day period. Although no changes were observed in the relative proportions of B, T, and Fc receptor-carrying lymphocytes, two T cell subpopulations, namely, the autologous rosette-forming cells and active rosette-forming cells, both exhibited significant increases. Significant increases were also demonstrated in the proportion of monocytes carrying Fc receptors and in the proportion of monocytes phagocytizing Latex beads. Although no consistent changes could be found in ADCC against the P 815 mastocytoma cell line, the SCMC against both the myeloid leukaemia line K 562 and the lymphoma line RAJI was found to be elevated as early as 6 hr post-vaccination. The possibility that the enhanced SCMC activity was induced in vivo by interferon was supported thus: 1) Enhancement of SCMC in vitro by interferon was abrogated by the vaccination. 2) Serum interferon determinations showed significant increases in parallel with the lack of in vitro SCMC enhancement.

Adult↗

Antibody-dependent monocyte-mediated cytotoxicity. Serial studies in acute myeloid leukaemia.

Antibody-dependent cytotoxicity mediated by purified monocytes was determined in 42 patients suffering from acute myeloid leukaemia (AML). Compared to 9 patients with acute bacterial infection and to 42 normal controls, patients with untreated AML exhibited deeply depressed monocyte cytotoxicity. Cytotoxicity was reduced in each of the cytomorphological subgroups of AML. Patients attaining remission showed the same cytotoxicity as patients not attaining remission. During remission monocyte cytotoxicity increased significantly, but normal function was not achieved. Patients receiving chemotherapy alone exhibited the same defective cytotoxicity as patients receiving chemotherapy plus immunotherapy with Corynebacterium parvum. The termination of maintenance chemotherapy after remission for 1 year did not normalize cytotoxicity. Also the cytotoxicity of normal monocytes was not affected by patient serum. It is suggested that the reduced monocyte cytotoxicity observed in AML is related to the leukaemic process. The lack of complete normalization during the remission may indicate the continuous presence of an intrinsic defect of monocytopoiesis.

Adolescent↗

Antibody-dependent monocyte-mediated cytotoxicity. The interference by platelets, immune complexes, and normal serum.

Monocyte mediated lysis of human type B-erythrocytes coated with heat-inactivated anti-B serum was measured as 51Cr-release. Preincubation of monocytes with heat-inactivated normal AB serum inhibited cytolysis while a strong stimulation of cytolysis was seen with fresh AB serum. These effects of serum were reversible upon cell washing. Preincubation of monocytes with hyperimmune human serum against type B erythrocytes did not alter the cytolysis. After incubation at 37 degrees C of monocytes with immune complexes formed of human albumin and rabbit anti-human albumin a dose-related inhibition of cytolysis was observed. This inhibition was equally expressed at different albumin to anti-albumin ratios. Pretreatment with immune complexes at 4 degrees C had the same effect on cytolysis as pretreatment at 37 degrees C. The effect of immune complexes on monocyte-mediated cytolysis was resistant to repeated cell washing. After incubation of pretreated monocytes at 37 degrees C for up to 18 h some of the inhibition disappeared, but without normalization. Platelet depletion of monocyte suspensions resulted in a significant increase of cytolysis, and addition of washed platelets reinduced a decreased of cytolysis, which correlated with the number of platelets added.

Animals↗