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S Hammarström

Publications and source records attributed to S Hammarström.

At least 145 records · Page 8Linked to original sources

Contractile activities of several cysteine-containing leukotrienes in the guinea-pig lung strip.

Eight biosynthetically formed cysteine-containing leukotrienes dose dependently (0.01-100 nM) contracted parenchymal strips of guinea-pig lung. The response to the leukotrienes was slow in onset, remarkably long-lasting and often tachyphylactic upon repeated administration. All the leukotrienes (LTC3, 8,9-LTC3, LTC4, 11-trans-LTC4, LTC5, LTD4, LTE4 and 11-trans-LTE4) were equally active full agonists for contraction, but approximately 5000 times as potent as histamine on a molar basis. Radiolabelled leukotriene C was insignificantly metabolized during the assay of contractile activity, indicating that the leukotrienes were active per se. The equipotency of LTC4, LTD4 and LTE4 also indicates that each of these three major constituents of slow reacting substance of anaphylaxis (SRS-A), may be considered a significant mediator of allergen-induced bronchoconstriction. In addition, the closely similar contractile activity of glutathionyl-substituted leukotrienes derived from polyunsaturated fatty acids other than arachidonic acid, suggests that they may contribute to bronchospastic disease under pathological and nutritional conditions promoting their formation.

Airway Resistance↗

Tumor localization of CEA-containing human tumors in nude mice by means of monoclonal anti-CEA antibodies.

Three different monoclonal antibodies (mabs) directed against conformation-dependent protein determinants in carcinoembryonic antigen (CEA) were evaluated for tumorimmunolocalization of CEA-containing human tumors grown in nude mice. The antibodies were of high affinity and of the IgG1 subclass. They did not react with non-specific cross-reacting antigen (NCA), biliary glycoprotein I (BGP I) or orosomucoid. 10-20 muCi (1-2 micrograms) of 131I-labelled mab was injected intraperitoneally into mice bearing heterografts of the CEA-containing human tumor cell lines LS 174T, Detroit 562 or HT-29 or into mice bearing grafts of the non-CEA-containing human tumor cell line RD. The concentration of radiolabelled mab in the tumor compared with the mean concentration in the mouse increased up to day 4 after injection. In contrast, the concentration ratios of radioactivity in the other tissues decreased with time. Excellent tumor localization was obtained with mab 38S1 in mice bearing LS 174T tumors. The concentration of radioactivity (cpm/g) tissue wet weight) was 24-390 times higher in the tumor than in the muscle. The difference between tumor and liver and between tumor and blood was 4-89 times and 2-25 times, respectively. A mean value of 40% of the total radioactivity in the mouse at day 4 was localized to the tumor. Mab 38S1 also showed positive tumor localization in mice carrying Detroit and HT-29 tumors. Means of 22% and 18% of the total radioactivity in the mouse at day 4 were found in these tumors, respectively. Mab 38S1 was, however, not enriched in the tumor of mice bearing the non-CEA-containing sarcoma RD. Furthermore, when LS 174T tumor-bearing mice were injected with normal mouse IgG, no enrichment of radioactivity in the tumor was seen. Positive tumor localization with mab 48 was obtained while mab 9 was not enriched in the tumor. Scanning pictures of LS 174T-grafted mice on day 4 after injection of 131I-mab 38S1 showed a definite radioactive spot corresponding to the tumor and in addition a spot corresponding to the liver or the heart.

Animals↗

Clinical evaluation of NCA in patients with chronic myelocytic leukemia.

NCA, a normal colon and granulocyte antigen, which has been found in large amounts in myelocytes and metamyelocytes and in smaller amounts in neutrophil granulocytes, was studied in 50 CML patients in various stages of the disease. Radioimmunoassay was used to demonstrate NCA in serum. Untreated CML patients had a mean level of 732 micrograms NCA/l, poorly controlled patients 421 micrograms/l and well-controlled patients 160 mu/l. These values differ significantly from the mean of healthy persons, which was 71 micrograms NCA/l. The serum NCA levels were related to the number of maturing myeloid cells in blood, and to the clinical course in the chronic phase of CML. In blast crisis low values with a mean of 109 micrograms NCA/l was found. Patients with ANLL had a low mean level, 50 micrograms/l. Low levels of NCA could not be attributed to antibodies to NCA. NCA is a normal myeloid differentiation antigen. Despite this, its occurrence in serum in leukemic patients differs from normal. This probably has to do with the abnormal amount as well as the release of NCA by leukemic maturing myeloid cells.

Antibodies↗

Distribution and metabolism of 3H-labeled leukotriene C3 in the mouse.

The distribution of [5,6,8,9,11,12-3H6]leukotriene C3 in mice was determined by whole body autoradiography of sagittal sections. Tritium was rapidly eliminated from the circulation by uptake in liver and excretion in bile as well as by renal uptake and excretion in urine. Chromatographic analyses of tritium in tissues and body fluids indicated that leukotrienes C3 and D3 constituted significant parts of the radioactivity in liver, bile, and small intestine 20 min after intravenous injection, whereas kidney contained leukotriene E3 and unidentified metabolites. Lung, pleural fluid, spleen, salivary glands, and connective tissue showed higher concentrations of tritium than blood. The radioactivity in lung consisted predominantly of leukotriene E3 with smaller amounts of leukotrienes C3 and D3.

Animals↗

Effect of leucotrienes C4, D4, prostacyclin and thromboxane A2 on isolated human cerebral arteries.

The effects of leucotrienes C4 (LTC4), D4 (LTD4), Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were studied on superfused human cerebral artery strips. LTC4 and LTD4 neither contracted nor relaxed the strips. PGI2 caused a dose-dependent relaxation from 0.2 nmol to 0.8 nmol. When given simultaneously with a vasoconstrictor substance, PGI2 had an almost complete inhibitory effect. TXA2 caused a dose-dependent contraction from 0.03 nmol to 0.15 nmol. Also, TXA2 was more potent than 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) with a contraction threshold of about 0.1 nmol. Prostaglandin E1 (PGE1), H2 (PGH2), and F2a (PGF2a) had contraction thresholds of about 1 nmol. Only a stable endoperoxide analogue (EPA), was more potent than TXA2, with a contraction threshold of 0.005 nmol. The possible role of these substances in producing ischaemic manifestations after subarachnoidal haemorrhage (SAH) is discussed.

Aged↗

Specificities and binding properties of eight monoclonal antibodies against carcinoembryonic antigen.

Eight different monoclonal antibodies against CEA were derived from fusions with spleen cells of mice immunized with highly purified CEA. All eight antibodies were IgG l, kappa and had isoelectric points between pH 6.5 and 7.5. They reacted strongly with native CEA, Smith degraded CEA (SI-stage) and CEAlow, only marginally with reduced and alkylated CEA and not at all with orosomucoid, indicating that they were directed against conformation dependent protein determinants. Two antibodies cross-reacted strongly with nonspecific cross-reacting antigen (NCA) while none of the antibodies cross-reacted with biliary glycoprotein I (BGP I). At least six different epitopes in the peptide moiety of CEA were recognized by this series of monoclonal antibodies. At least two of these appeared to occur twice in the molecule, possibly indicating that CEA contains two or more homology regions. The affinity constants of three of the CEA-'specific' antibodies were found to be very high, e.g. 1.2, 3.3, and 7.4 X 10(8) M-1, respectively.

Animals↗

Mitogenic leukoagglutinin from Phaseolus vulgaris binds to a pentasaccharide unit in N-acetyllactosamine-type glycoprotein glycans.

The carbohydrate binding specificity of leukoagglutinin (La; Phaseolus vulgaris isolectin L4) was studied by using quantitative precipitation and precipitation-inhibition. A series of purified glycopeptides and synthetic oligosaccharides were used as inhibitors. The minimal structural unit required for La binding was the disaccharide GlcNac(1 leads to beta 2)Man. Additions for this basic unit of different sugar residues gave a positive or negative contribution to binding. The most complementary structure was the pentasaccharide (formula: see text). This pentasaccharide units occurs in tetraantennary N-acetyllactosamine-type glycoprotein glycans. Glycoproteins containing such structures were accordingly precipitated by La. Selected glycopeptides and oligosaccharides were also tested as inhibitors of La-induced DNA synthesis in human lymphocytes. The pattern of inhibition was essentially the same as that obtained by precipitation-inhibition, indicating that binding to lymphocytes via the carbohydrate binding site of the lectin is an essential step in the activation process.

Binding Sites↗

Localization of T-lymphocyte areas in human lymphoid tissues by fluorochrome-labelled Helix pomatia A haemagglutinin.

Fluorochrome-labelled Helix pomatia A haemagglutinin (HP) stained T-dependent areas in cryostat tissue sections of human lymph node, tonsil, and spleen and thymocytes within thymic medulla but not within thymic cortex. Neuraminidase treatment of the tissue section was a prerequisite for the positive cell staining. The staining was cell-membrane-associated, and the histological pattern was essentially the same as that observed in parallel sections treated with monoclonal antibodies to T cells (OKT3, Leu-1). In addition, blood vessel walls and connective tissue were also stained by HP conjugates. The latter staining was independent of neuraminidase treatment, resistant to alpha-galactosidase treatment and was not blocked by pretreatment with anti-fibronectin antibody. Body types of staining reaction were specific inasmuch as unlabelled HP and the competitive sugar hapten N-acetyl-D-galactosamine blocked the reaction, Frozen, formalin-fixed tissue sections showed the same stainability and reaction pattern as unfixed sections.

Animals↗