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Biomedical subjects

R Fäldt

Publications and source records attributed to R Fäldt.

33 records · Page 2Linked to original sources

Antibodies to human adult T cell leukaemia virus type I associated antigens in Swedish leukaemia patients and blood donors.

Antibodies to antigens associated with human T cell leukaemia virus type I (HTLV I) in Swedish adult leukaemia patients and blood donors were sought with a sensitive screening test using membrane antigen prepared from virus producing cells (MA-ELISA). Four persons (one ALL, one AML and two healthy blood donors) out of 483 persons tested reacted in the test. However, they were negative in the more specific anti-p19 and anti-whole virion ELISA tests. The prevalence of sera with definite anti-HTLV I activity seems to be very low in Sweden. The finding of four MA-ELISA positive persons needs further investigation.

Adult↗

Effect of latex-stimulated granulocytes on platelet aggregation in man.

The effect of granulocytes on human platelet aggregation was investigated in vitro. Platelet function was assayed by photometric technique. Incubation of platelets with latex-stimulated granulocytes for 1 h at room temperature resulted in total inhibition of arachidonic acid-induced platelet aggregation. ADP-induced platelet aggregation was suppressed, lacked secondary wave and was pursued by swift disaggregation. Platelet aggregates induced by collagen dispersed faster under the influence of stimulated granulocytes. The present results indicate that granulocytes may play a role in the hemostatic mechanism in man.

Adenosine Diphosphate↗

Beta blockers and loss of hearing.

Loss of hearing in a 43 year old man during treatment with metoprolol was dose related and disappeared within a few months after the drug had been stopped. The hearing impairment was of mixed type, with an air bone gap without any disorder of the middle ear observable by conventional clinical methods. Similar scattered reports from international sources on loss of hearing during treatment with beta blockers are also presented.

Adult↗

Complete remission in a patient with acute myelogenous leukemia treated with leukocyte alpha-interferon and cimetidine.

A 76-year-old woman with acute myelogenous leukemia with approximately 65% myeloblasts on bone marrow examination was treated daily with a combination of 4 megaU of leukocyte interferon IM and 1,000 mg cimetidine PO. During therapy there was a gradual decrease of bone marrow myeloblasts down to 9% and a normalization of peripheral white blood cells. The treatment was discontinued after 6 weeks because of increasing fatigue and anorexia. The general condition improved greatly during the following weeks and the patient entered complete remission, which has continued for 6 months so far. In the course of therapy there was a gradual appearance of antibodies showing a selective binding capacity to autochthonous leukemic cells with no tendency to increased binding to remission cells. The aim of this report is to stimulate a further evaluation of this form of therapy in additional AML patients whenever this might be justified as an alternative to conventional chemotherapy.

Aged↗

Decreased responsiveness to immune complexes of granulocytes from patients with acute leukemia in remission demonstrated by microcalorimetry.

Functional activity of granulocytes from healthy individuals and from patients with acute leukemia in remission was studied. The increase of heat production rate (metabolic activity) after stimulation of the blood cells with in vitro formed immune complexes was measured by microcalorimeters of heat conduction type. It was demonstrated that increased heat production rate after exposure to immune complexes was significantly lower (p less than 0.0005) in 9 patients with acute leukemia with a remission duration of less than 6 months than in 25 healthy volunteers.

Acute Disease↗

Heat production rate in polymorphonuclear granulocytes from patients with acute myelogenous leukaemia and healthy individuals.

Heat production rate in polymorphonuclear granulocytes (PMN) from 18 AML patients and 21 healthy individuals was measured using microcalorimetry. An increased PMN heat production rate was found in most AML patients at diagnosis and during the first 6 months of remission. In 7/7 patients showing values above the normal mean level the heat production rate decreased during sequential analysis. The increased PMN heat production rate is serum dependent and leukaemic sera induced increased calorimetric values also in PMN from healthy donors. This effect was not due to heat labile complement factors.

Blood Donors↗

A 125I-protein A-binding assay detecting antibodies to cell surface antigens. Evidence for the presence of specific antibodies against leukemia-associated antigens in human leukemias.

A 125I-protein A-binding assay detecting antibodies to cell surface antigens on human blood cells was developed and evaluated using sera from multitransfused nonleukemic patients sensitized against HLA antigens. The binding assay was found to be reproducible and more sensitive than conventional HLA testing. Seven patients with acute myelogenous leukemia and two patients with acute lymphoblastic leukemia successfully treated by chemotherapy were then investigated. Sera from seven of the patients studied in partial or complete remission demonstrated significant binding to autochthonous leukemic cells obtained from bone marrow or peripheral blood. In two cases sera taken during the leukemic stage demonstrated the most pronounced binding to the patients' own leukemic cells. Sera from four patients with demonstrable significant binding to autochthonous leukemic cells failed to bind to autochthonous remission cells when both types of target cells were tested in parallel. Differences in serum concentrations of IgG, IgA, and IgM were not the cause of the demonstrated increased binding of leukemic sera to autochthonous target cells. We propose that the 125I-protein A-binding assay presented in this paper detects antibodies reacting selectively with acute leukemia cells.

Adult↗

Heat production in different populations of human blood cells exposed to immune complexes in vitro: the importance of the Fc parts of immunoglobulins and the influence of active complement.

By use of a batch microcalorimeter of the thermopile type, heat production was measured in isolated populations of human peripheral blood cells exposed to defined immune complexes formed in vitro. It was found that most of the heat production recorded in whole blood after admixture of immune complexes occurs in the granulocytes. Under these conditions small but constantly higher activation values were found in the absence of active complement. It was shown that complexes consisting of antigen and F(ab)2 fragments prepared from the specific antibodies were able to initiate heat production in the cells only in the presence of active complement. These experiments indicate that immune complexes are able to induce increased heat production in the cells either by binding to Fc receptors or by activation of complement through the alternative pathway and subsequent binding of the generated C3b to C3b receptors on the heat-producing cells.

Antigen-Antibody Complex↗

Possibly specific immune complexes in sera of patients with untreated acute myelogenous leukemia.

Eleven patients with acute myelogenous leukemia (AML) in the acute stage of the disease were studied. Sera of seven patients were assayed for complement-dependent cytotoxicity to autochthonous AML cells and sera of four patients were tested with allogeneic target cells before and after ultrafiltration at low pH. No specific cytotoxic activity could be detected in any untreated sera. Ultrafiltration at low pH led, however, to the appearance of a significant cytotoxic activity in all of seven autochthonous and in three of four allogeneic combinations. Identical treatment of control AB sera did not result in any similar activity. The results show that potentially cytotoxic antibodies to leukemia-associated antigens are present in the acute stage of acute myelogenous leukemia. However, they do not express complement-dependent cytotoxicity in untreated sera. After ultrafiltration at low pH significant complement-dependent cytotoxicity was detectable in most of the sera. One possible explanation is that cytotoxic antibodies to leukemia-associated antigens are present in the form of circulating immune complexes. Splitting of them at low pH and elimination of the antigen component might result in an increased amount of free cytotoxic antibodies.

Antibody Specificity↗

A new approach to detection of antigen-antibody complexes by microcalorimetric measurements of heat production in blood cells.

Using batch microcalorimeters of the thermopile conduction type, heat production was measured in human blood in the presence of defined antigens and their specific antibodies. A large increase in heat production, reflecting increased metabolic activity in the blood cells, was found when antigens and specific antisera at certain antigen-antibody proportions were mixed with the blood. The reproducibility and specificity of the method were found to be very good. The present results indicate that calorimetry may be a useful technique for detection of antigen-antibody complexes.

Animals↗

Demonstration of antibody-associated cellular cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy.

This study demonstrates that a cytotoxic serum reactivity not requiring the presence of complement appears in the sera of patients with acute myelogenous leukemia. The reaction is detected upon short-term incubation of sera in vitro with autochthonous mononuclear white blood cells from peripheral venous blood of patients at the acute stage of the disease. This reactivity was demonstrated in 18/18 patients. Generally, the cytotoxicity was low in patients at the acute stage of the disease, but increased after chemotherapy and reached the highest level at the onset of clinical remission or just before. No cytotoxicity could be demonstrated against autochthonous remission white blood cells. The serum activity could be absorbed and eluted from protein A-sepharose CL-4B and was recovered in the 7S-fraction of the sera after gel filtration on Sephadex G-200 and ion exchange chromatography. This indicates that the demonstrated cytotoxicity is due to immunoglobulins of IgG-class. It is believed that Fc-receptor-bearing cells present in the target cell preparations function as effector cells. The reaction is designated antibody-associated cellular cytotoxicity (AACC).

Adult↗

Tumor-associated humoral cytotoxicity in patients with acute myelogenous leukemia before and after chemotherapy.

Sera of eight unselected adult patients with acute myelogenous leukemia obtained before and after chemotherapy were repeatedly tested for specific complement-dependent cytotoxicity against autochthonous peripheral white blood cells from the acute leukemia stage and from the remission stage, respectively. Complement-dependent cytotas demonstrated in all of the eight patients, while none of three patients' sera were reactive against white blood cells from the remission stage tested in parallel. The cytotoxicity was increased after chemotherapy, also in those patients in whom remission was not achieved.

Adult↗