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Biomedical subjects

R Fäldt

Publications and source records attributed to R Fäldt.

At least 19 recordsLinked to original sources

Redistribution of blood flow in the cerebral cortex of normal subjects during head-up postural change.

Regional cerebral blood flow was measured in 21 normotensive subjects during supine rest and during head-up tilt to 70 degrees. The results showed significant and consistent regional cerebral blood flow changes in the frontal areas with lower relative flow distribution values (percentage of mean flow) during head-up tilt than during supine rest. The lower frontal flow distribution values during tilt were not related to habituation, to repeated measurements, or to the estimated level of arterial CO2 which was derived from expired end-tidal CO2 levels. None of the subjects had orthostatic hypotension and there was no significant difference in mean hemispheric blood flow between lying down and standing up. There was no significant gender difference in regional cerebral blood flow, although female subjects tended to have higher mean hemispheric flow than males in both postures. It remains to be established whether the flow decreases in the frontal cortex are caused by cerebral functional factors or by haemodynamic mechanisms.

Adult

Inhibition of platelet aggregation by granulocytes stimulated during experimental trauma.

The effect of granulocytes, stimulated in vivo by standardized soft tissue trauma, on the aggregation of autologous platelets in vitro, was studied in the pig. Platelet aggregation induced by ADP and arachidonic acid was inhibited when platelets harvested before trauma were incubated with granulocytes obtained 5 min after trauma. The granulocytes were separated from the platelets during the incubation by enclosure in dialysis tubes. Platelet inhibition was evident when the cell cohorts were suspended in cell-free medium as well as in autologous plasma extracted before trauma. In addition, incubation of platelets harvested before trauma with plasma obtained after trauma decreased platelet aggregation. In conclusion, granulocytes stimulated in vivo inhibited platelet function in vitro. Platelet inhibitory activity was shown to be related with the granulocytes per se, but also with factors present in plasma after trauma.

Adenosine Diphosphate

Inhibition of platelet aggregation by myeloid leukaemic cells demonstrated in vitro.

The effect of myeloid leukaemic cells, cells of the promyelocytic cell line HL-60 and normal polymorphonuclear granulocytes (PMN), enclosed in dialysis tubes, on the aggregation of allogeneic normal platelets after induction with arachidonic acid (AA) and with adenosine diphosphate (ADP) was investigated in vitro. Inhibition of aggregation was seen after preincubation of the platelets with leukaemic blood or bone marrow cells from 7/14 patients belonging to various FAB groups and with HL-60 cells, but not with normal PMN (14/14 cases). A dose-dependent inhibition was seen after lysis of some leukaemic cells with anti-human rabbit antiserum and active complement. Lysis of normal PMN inhibited platelet aggregation slightly and inconstantly and only at higher cell concentrations. Platelet inhibitory activity was not related to a higher rate of metabolism of the leukaemic cells which inhibited platelet aggregation since they did not differ from the cells not inhibiting aggregation with respect to heat production. Neither was a non-specifically increased cell membrane permeability the cause of the release of platelet inhibitory factor(s) since the release of 51Cr-labelled leukaemic cells was not related to the inhibition of platelet aggregation.

Adenosine Diphosphate

Differential pattern of oncogene and beta-actin expression in leukaemic cells from AML patients.

The presence of mRNA hybridizing to five oncogene (fos, mos, myc, sis, abl) and a beta-actin probe(s) was studied with a semiquantitative dot-blot procedure in eight AML patients. Around 10(7) leucocytes, corresponding to 1-10 ml blood, sufficed for the analysis. Each patient, regardless of the FAB group, exhibited a distinct pattern of oncogene or beta-actin expression. Especially strong signals were obtained with the beta-actin probe in two patients and with the fos probe in three patients. The findings underscore the heterogeneity of AML, either present from the first step towards malignancy or arising during the progression of the disease. The pattern of oncogene expression in leukaemic cells studied in routine blood samples may become an additional means for classification and follow-up of AML patients.

Actins

Abnormal granulocyte functions in autoimmune disorders demonstrated by microcalorimetry.

Heat production by polymorphonuclear granulocytes (PMN) was assayed in 14 patients suffering from diseases known to be associated with circulating immune complexes (CIC) and in 10 healthy blood donors. The patients' PMN produced significantly more heat than the normal PMN when the cells were suspended in autologous plasma (23.8 +/- 3.9 pW/cell vs. 18.1 +/- 1.9 pW/cell, p less than 0.0005), but not when the cells were suspended in tissue culture medium (5.6 +/- 1.2 pW/cell vs. 5.6 +/- 0.8 pW/cell, p greater than 0.05). After mixing with IgG-coated latex particles the heat production by patients' PMN were significantly less stimulated than that of normal PMN when the cells were suspended in autologous plasma (42 +/- 13% vs. 75 +/- 22%, p less than 0.0005), but not when the cells were suspended in tissue culture medium (82 +/- 24% vs. 83 +/- 22%, p greater than 0.05). The increase of heat production by normal PMN after stimulation with IgG-coated latex particles was significantly lower when the cells were preincubated with heat aggregated human gammaglobulin compared to that obtained when the cells were preincubated in saline (11 +/- 10% vs. 51 +/- 11%, p less than 0.001). This finding shows that the increased PMN heat production which occurs after binding of the IgG-coated particles is mediated via Fc receptors. A plasma factor(s), possibly circulating immune complexes, can explain the abnormal PMN functions in the patients.

Adult

Use of microcalorimetry in analysing the kinetics of ADCC.

Microcalorimetry was found to be a useful technique for the demonstration of antibody-dependent cellular cytotoxicity (ADCC) against human melanoma cells mediated by a heterologous rabbit antiserum and two monoclonal antibodies in combination with human peripheral blood lymphocytes as effector cells. The rabbit antiserum and the monoclonal IgG3 antibody 2B2 directed against the GD3 ganglioside expressed cell-inhibitory effects resulting in a decreased heat production rate over 2-18 h of incubation. The 4.2 monoclonal IgM antibody to GD3 had no similar cell-inhibitory effect. In contrast, the 4.2 antibody expressed a much stronger effect than 2B2 in tests for complement-dependent cytotoxicity. The kinetics of these effects were quite reproducible. It is concluded that microcalorimetry is a sensitive and particularly suitable method for the analysis of cytotoxicity kinetics.

Animals

Demonstration of antibodies binding to autologous and allogeneic leukemic cells in childhood ALL. Evidence for a common ALL antigen(s).

The humoral immune response to autologous leukemic cells was investigated in childhood ALL using a 125I protein A binding assay. In 5/7 patients antibodies were demonstrated at diagnosis and in 3/7 cases also after chemotherapy. Sera from 2/3 patients, which bound significantly to autologous leukemic cells, did not bind significantly to autologous remission cells. In allogeneic experiments sera bound significantly to ALL leukemic cells (6/7 positive combinations), but not to AML leukemic cells (8/8 negative combinations). We propose that ALL sera contain antibodies binding to autologous leukemic cells and that they are directed against a common ALL antigen(s).

Antibodies, Neoplasm

Differentiation of myeloid leukemic cells in vitro demonstrated by microcalorimetry: stimulation of leukemic and remission cells by IgG-binding Fc receptors.

Interaction of immunoglobulin G (IgG)-coated latex particles with Fc receptors on myeloid leukemic blood cells and on polymorphonuclear granulocytes (PMN) from remission patients and healthy blood donors was investigated using microcalorimetry. The induced heat production by leukemic cells from 13 patients with the M2, M4 and M5 FAB groups (French-American-British classification) of acute myeloid leukemia (AML) was significantly higher than that of leukemic cells from 7 patients with the M1 FAB group (p less than 0.005) and mononuclear blood cells from 10 healthy individuals (p less than 0.005). The values were similar for PMN from 10 remission patients and 10 healthy blood donors. After incubation of M1 cells in vitro for 24-30 h at 37 degrees C the heat production induced by IgG-coated latex particles by the cells increased significantly, indicating the appearance of Fc receptors for IgG. In addition, the heat production by unstimulated M2, M4 and M5 cells was significantly higher than that by unstimulated M1 cells (p less than 0.005) and normal mononuclear cells (p less than 0.0005). The heat production by unstimulated PMN suspended in tissue culture medium was similar in remission patients and healthy blood donors.

Calorimetry

Microcalorimetry as a tool for the detection of complement-dependent cytotoxicity.

Microcalorimetry using a 4-channel static ampoule microcalorimeter of thermopile type has been evaluated as a tool for the detection of complement-dependent cytotoxicity against the surface antigens of living cells. Cytotoxic reactions mediated by a rabbit antiserum against human white blood cells and by 2 different monoclonal antibodies recognizing a melanoma-associated antigen on a human melanoma cell line were studied. The cytotoxic reactions were registered as a decrease of the heat production rate when the cells were exposed to antibodies in the presence of active complement as compared to the heat production rate of the cells exposed to the same antibodies in the presence of inactive complement. This investigation shows that microcalorimetry can be used as a highly sensitive method for the detection of complement-dependent immune reactions, detecting antibody dilutions higher than 10(-5). It also indicates that microcalorimetry may become a particularly important technique in the analysis of the kinetics of cytotoxic immune reactions in vitro.

Animals

Immunoglobulin G antibodies binding to a synthetic peptide deduced from the nucleotide sequence of the env gene of HTLV I in patients with leukemia and rheumatoid arthritis, HLA sensitized persons and blood donors.

A synthetic pentadecapeptide preparation, env 406-420, with an amino acid sequence deduced from the envelope glycoprotein gene of human T cell leukemia virus type I (HTLV I), was used as the antigen in an enzyme immunoassay for immunoglobulin G antibodies, exploring its usefulness for seroepidemiological purposes. The frequency of reactivity in the test groups, presented in decreasing order was: patients with rheumatoid arthritis; multitransfused nonleukemic patients; Japanese cases of adult T cell leukemia (ATL); HLA sensitized persons; Swedish cases of adult acute leukemia; and Swedish blood donors. Three American cases of ATL and 12 HTLV I seropositive monkeys did not react. In RF positive sera from patients with rheumatoid arthritis, no quantitative correlation between RF activity and anti-env 406-420 activity was seen. Anti-env 406-420 positive sera did not react or reacted only weakly with four control peptide preparations with different amino acid sequences. The experience with oligopeptide serology still is limited. Our results illustrate that unexpected cross-reactions which are hard to interpret can occur. Although absorption experiments indicated an HTLV I specific component of the reactivity, antibodies against epitopes of allo- and auto-immune specificity may also have participated.

Arthritis, Rheumatoid

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