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S Hammarström

Publications and source records attributed to S Hammarström.

At least 109 records · Page 6Linked to original sources
PubMed1986

IgE-mediated activation of human heart in vitro.

We used human cardiac tissue from the right atrial appendages of patients undergoing corrective heart surgery to study content and de novo synthesis of mediators in the human heart. Human heart tissue contained 1.7 +/- 0.1 micrograms/g wet weight of histamine (mean +/- S.E.M.) and spontaneously produced 6-keto-PGF1 alpha (38.4 ng/g wet weight/min), PGF1 alpha (1.9 ng/g wet weight/min), PGE (1.7 ng/g wet weight/min) and thromboxane B2 (TxB2) (1.7 ng/g wet weight/min). Spontaneous release of PGD2, leukotriene C4 and histamine was negligible. Rabbit anti-human IgE (1-10 micrograms/ml) dose-dependently induced the release of histamine (5 to 15% of the total histamine content) and of PGD2 (5 to 100 ng/g of wet tissue). The effect of anti-IgE was dose-related and reached a maximum after 30-45 min of incubation. A significant linear correlation (rs = 0.90; p less than 0.001) was found between de novo synthesis of PGD2 and the secretion of histamine induced by anti-IgE challenge of human heart. These results support the concept that PGI2 is the main, but not the sole, product of arachidonic acid metabolism synthesized by human heart in vitro. Additionally, anti-IgE challenge of human heart in vitro induces the release of histamine and PGD2. The local concentrations of these mediators appear high enough to play some role in the modulation of several cardiac functions in vivo.

Animals↗
PubMed1986

Epitope specificity and cross-reactivity pattern of a large series of monoclonal antibodies to carcinoembryonic antigen.

Monoclonal antibodies (MAbs) were produced against purified carcinoembryonic antigen (CEA) from liver metastases of colo-rectal and lung adenocarcinoma. Three and eight anti-CEA MAbs from the two groups were analyzed in detail. All antibodies were IgG1. With one exception they recognized epitopes present on all eight individual CEA preparations investigated irrespective of whether they were from colo-rectal or lung carcinoma. The exceptional MAb reacted with an epitope present on most but not all CEA preparations. With two, or possibly three, exceptions the MAbs recognized conformation dependent epitopes in the peptide moiety of CEA. One MAb reacted strongly with reduced and carboxymethylated CEA but only weakly with native CEA. Four MAbs appeared to be CEA-specific in that they did not react with any of the known CEA-cross-reactive substances including nonspecific cross-reactive antigen of 160,000 mol. wt (NCA-160). A total of nine different epitopes were detected in native CEA using this and our previous series [Hedin A., Hammarström S. and Larsson A. (1982) Molec. Immun. 19, 1641] of anti-CEA MAbs. With one exception practically all molecules (70-90%) in purified CEA preparations contained these epitopes.

Antibodies, Monoclonal↗
PubMed1986

Prostaglandin sensitivity of the PHA-response of blood lymphocytes following radiation therapy for breast cancer.

The reduction of mitogen responses of blood lymphocytes which occur after radiation therapy for breast cancer, known to be largely due to inhibitory monocytes, can partly be reverted by indomethacin which is an inhibitor of prostaglandin (PG) synthesis. This may indicate that PG-synthesis by blood monocytes is increased after irradiation or that PG-sensitivity of the lymphocyte population is increased. To test the latter possibility the sensitivity of the PHA-response of blood lymphocytes to varying concentrations of PGE2 and PGD2 was examined in 15 patients with breast cancer before and up to 6 months after local radiation therapy (46 Gy). The results showed that the sensitivity of the PHA-response was not significantly changed after treatment suggesting that the immunosuppression observed after irradiation is partly due to an increased production of PGs rather than an increased PG-sensitivity of lymphocytes.

Adult↗
PubMed1986

Metabolism and excretion of cysteinyl-leukotrienes.

In vitro and in vivo experiments have demonstrated that a major pathway of metabolism of the glutathione containing leukotrienes involves modifications of the tripeptide substituent. The metabolic alterations are initiated by elimination of the N-terminal gamma-glutamyl residue, catalyzed by the enzyme gamma-glutamyl transferase. This reaction is followed by hydrolysis of the remaining peptide bond resulting in elimination of the C-terminal glycine residue. The enzyme catalyzing the latter reaction is a membrane bound dipeptidase which occurs in kidney and other tissues. The product formed by these reactions, leukotriene E4, has been tentatively identified as a urinary metabolite in man following intravenous administration of leukotriene C4. In rats, two major fecal metabolites of leukotriene C4 were characterized as having the structures N-acetyl leukotriene E4 and N-acetyl 11-trans leukotriene E4. These compounds are formed from leukotriene E4 and 11-trans leukotriene E4 in reactions with acetyl coenzyme A. A membrane bound enzyme, present in liver, kidney and other tissues, catalyzes these reactions.

Animals↗
PubMed1986

Polyclonal and monoclonal anti-CEA antibodies in immunolocalization of colorectal cancer.

Antibodies to carcinoembryonic antigen (CEA) from sheep and monkey were immunoadsorbent purified. Mouse monoclonal antibody (MAb) anti-CEA I-38S1 and Fab fragments of this antibody were prepared from mouse ascitic fluid. The IgG preparations were labelled with 123I or 131I, the Fab fragments with 131I. The antibody reactivity was unchanged after labelling. Patients with advanced colorectal carcinomas received an intravenous injection of 50-200 MBq 123I or 30-160 MBq 131I coupled to 250-500 micrograms antibody or antibody fragment. Patient examinations were performed using emission tomography (SPECT) and/or conventional gamma camera scintigraphy. The specific localization of labelled anti-CEA to tumor was compared to known tumor localized by CAT-scan, other x-ray methods or laparotomy, 50% of known tumors were accurately localized with sheep anti-CEA. In contrast, 70-80% of known tumor sites were correctly localized with polyclonal monkey anti-CEA antibodies, with monoclonal anti-CEA antibodies or with Fab fragments of the latter. A few previously unknown tumors were detected.

Antibodies, Monoclonal↗
PubMed1986

Improved radioimmunolocalization of carcinomas using Fab fragments with anti-CEA specificity.

A model system with human colonic grafts containing carcinoembryonic antigen (CEA) in nude mice was used to improve specificity and sensitivity of the radioimmunolocalization method. Monoclonal antibody MAb I-38S1 and monkey anti-CEA appeared to have high in vitro and in vivo specificity. Fab fragments of MAb I-38S1 improved localization ratios. A reduced time for optimal immunolocalization was obtained with Fab compared with MAb of the same specificity. Combinations of Fab:s, vasoactive compounds or anti-IgG treatment to reduce background levels did not further improve speed of localization or sensitivity.

Alkaline Phosphatase↗
PubMed1985

In vivo metabolism of leukotriene C4 in man: urinary excretion of leukotriene E4.

Five - 20 nmoles of [5,6,8,9,11,12,14,15-3H8]leukotriene C4 was injected into three male volunteers. Forty-eight percent of the administered 3H was recovered from urine and 8% from feces, within a 72 hr period. Of the total urinary radioactivity 44% was excreted during the first hour after injection. This activity was mainly found in one compound, designated "I". The radioactivity excreted into urine later than one hour after injection, consisted partly of Compound I and two additional components, and partly of polar, non-volatile material. Compound I was identified as leukotriene E4 by UV-spectroscopy and cochromatographies in three high performance liquid chromatography systems with synthetic reference compounds. A total of 13% of administered radioactivity was excreted in urine as leukotriene E4.

Adult↗
PubMed1985

Leukotriene C4 formation catalyzed by three distinct forms of human cytosolic glutathione transferase.

The ability of three distinct types of human cytosolic glutathione transferase to catalyze the formation of leukotriene C4 from glutathione and leukotriene A4 has been demonstrated. The near-neutral transferase (mu) was the most efficient enzyme with Vmax= 180 nmol X min-1 X mg-1 and Km= 160 microM. The Vmax and Km values for the basic (alpha-epsilon) and the acidic (pi) transferases were 66 and 24 nmol X min-1 X mg-1 and 130 and 190 microM, respectively. The synthetic methyl ester derivative of leukotriene A4 was somewhat more active as a substrate for all the three forms of the enzyme.

Arachidonic Acids↗
PubMed1985

The large sialoglycoprotein of human lymphocytes. I. Distribution on T and B lineage cells as revealed by a monospecific chicken antibody.

Chickens were immunized with highly purified large sialoglycoprotein of human lymphocytes (L-LSGP; gp 150) which was isolated from neuraminidase-treated normal peripheral blood lymphocytes by affinity chromatography to HP-Sepharose and further purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antibodies isolated from plasma and egg yolk were highly specific for desialylated L-LSGP (apparent molecular mass approximately 150 kDa). The antigenic sites recognized by the antibodies are probably located in the peptide moiety of the molecule since antibody binding to lymphocytes was not inhibited by a variety of different sugars or abrogated by absorption on various erythrocytes. In immunofluorescence experiments, greater than or equal to 75% of neuraminidase-treated thymocytes and peripheral blood lymphocytes, virtually all E+ cells and T4+ or T8+ T chronic lymphocytic leukemia (CLL) cells were stained by anti-gp 150. A small fraction (approximately 10%) of thymocytes and a larger fraction (greater than or equal to 30%) of T CLL cells in some patients were stained before neuraminidase treatment. Thymocytes appear to contain considerably lower amounts of a less sialylated form of L-LSGP than peripheral blood lymphocytes. In contrast to blast cells of 5-day concanavalin A or leucoagglutinin cultures (greater than or equal to 90% anti-gp150+) only about 50% of the blast cells generated in 5-day mixed leukocyte cultures were anti-gp150+. The large majority (greater than or equal to 75%) of both the anti-gp150+ and anti-gp150- cells were T3+ and T11+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The large sialoglycoprotein of human lymphocytes. II. Biochemical features.

Large sialoglycoprotein of human lymphocytes (L-LSGP) from thymocytes and from peripheral blood lymphocytes (PBL) of normal donor and of B chronic lymphocytic leukemia (CLL) patients was purified by affinity chromatography to Maclura pomifera agglutinin (MPA)-Sepharose followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). L-LSGP from the three different sources was very similar in amino acid composition. It contained a high proportion of acidic and hydroxy amino acids and also significant amounts of cysteine. No reduction in mobility in SDS-PAGE was noted for unreduced L-LSGP. The molecule may already in its native form have an extended conformation containing either free sulfhydryl groups or small S-S loops not affecting mobility in SDS-PAGE. L-LSGP was found to be highly glycosylated, the thymocyte glycoprotein containing somewhat less carbohydrate by weight (44%) than that of PBL (normal PBL 53% and B CLL 52%). This was due primarily to a lower content of sialic acid. The molecules contained mannose, galactose, N-acetyl galactosamine, N-acetylglucosamine and sialic acid in molar ratios 1.0:3.0:1.1:1.2:1.3 (thymocyte L-LSGP), 1.0:3.8:1.2:1.0:1.7 (PBL L-LSGP) and 1.0:3.5:2.2:1.3:2.8 (B CLL L-LSGP). The weak interaction of L-LSGP with lentil lectin, concanavalin A (Con A) and leucoagglutinin (La), its unchanged mobility in SDS-PAGE after tunicamycin treatment and its high amount of hydroxy amino acids suggest that most carbohydrate chains are O-glycosidically linked to the peptide chain. Native as well as Nase-treated L-LSGP show size microheterogeneity. This is probably due to small chemical differences in the L-LSGP molecules from different lymphocyte subsets.

Amino Acids↗
PubMed1985

Metabolism of leukotrienes.

The in vitro metabolism of leukotriene B4 is initiated by omega-hydroxylation. This reaction is followed by oxidation of the omega-hydroxyl group to a carboxyl group. In vivo extensive beta-oxidation occurs and the main excreted products after administration of leukotriene B4 are water and carbon dioxide. Experiments performed in vitro and in vivo have demonstrated that a major pathway of metabolism of the glutathione containing leukotrienes involves modifications of the tripeptide substituent. The metabolic alterations are initiated by enzymatic elimination of the N-terminal gamma-glutamyl residue, catalyzed by the enzyme gamma-glutamyl transferase. This reaction is followed by hydrolysis of the remaining peptide bond resulting in elimination of the C-terminal glycine residue. The enzyme catalyzing the latter reaction is a membrane bound dipeptidase which occurs in kidney and other tissues. The product formed by these reactions, leukotriene E4, has been tentatively identified as a urinary metabolite in man following intravenous administration of leukotriene C4. In rats, the two major fecal metabolities of leukotriene C4 were characterized as being N-acetyl leukotriene E4 and N-acetyl 11-trans leukotriene E4. These compounds are formed in reactions between leukotriene E4 or 11-trans leukotriene E4 and acetyl coenzyme A. The reactions are catalyzed by a membrane bound enzyme present in liver, kidney and other tissues.

Animals↗
PubMed1985

Leukotrienes C4, D4 and E4 cause widespread and extensive plasma extravasation in the guinea pig.

Intravenous injection of leukotriene C4 (1 nmol X kg-1) caused substantial plasma exudation in anesthetized guinea pigs, as evidenced by marked hemoconcentration 15% in 5 min) and significant extravasation of Evans blue. Fluorometric quantitation of Evans blue content in 38 selected tissues documented that leukotriene C4 caused significant plasma extravasation throughout the body, except for the brain, stomach, duodenum, colon and gonads. In particular, the respiratory and the uro-genital tracts, but also the conjunctiva, the esophagus, the bile ducts and the umbilical ligaments, were very sensitive to the edema-promoting effect of leukotriene C4. Intravenous injection of leukotriene D4 (1 nmol- X kg-1) or E4 (5 nmol X kg-1) evoked plasma extravasation with a distribution and magnitude that was similar to that induced by leukotriene C4. It is concluded that the three major constituents of slow reacting substance of anaphylaxis (SRS-A), leukotrienes C4, D4 and E4, cause a generalized and extensive plasma exudation that is consistent with the proposal that these leukotrienes are important mediators of inflammation.

Animals↗
PubMed1985

Leukotrienes and myometrial activity of the term pregnant uterus.

Biopsies from different segments of the pregnant human uterus were superfused in organ chambers and contractile activity was registered. Leukotriene C4(LTC4) caused inhibition of spontaneous but not noradrenaline induced contractile activity in strips from the cervix. This effect occurred both in early pregnancy and at term. However, the lower and the upper uterine segment of the term pregnant uterus did not respond to LTC4. The results represent a documentation of the segmental differentiation in the uterine response to eicosanoids.

Cervix Uteri↗
PubMed1985

A new surface marker on equine peripheral blood lymphocytes. I. Subpopulations of lymphocytes with receptors for Helix pomatia A hemagglutinin (HP).

Untreated and neuraminidase-treated equine peripheral blood lymphocytes were analysed for binding of the A hemagglutinin of the snail Helix pomatia (HP). For optimal staining by direct immunofluorescence, the concentration of neuraminidase had to be increased as compared to that needed for other species. Moreover, higher concentrations of HP were required for optimal staining of equine lymphocytes as compared to lymphocytes from other species. Even so, the maximal number of equine lymphocytes exhibiting positive staining was only about 20%. No, or very few, HP-positive lymphocytes were seen when neuraminidase treatment was omitted. However, when the more sensitive method of indirect immunofluorescence was used, approximately 60% of the lymphocytes were HP positive without prior treatment with this enzyme. Neuraminidase treatment significantly increased this figure to about 75%. In all instances, HP binding was specific since it was inhibited by the competitive sugar hapten N-acetyl-D-galactosamine (D-GalNAc) while addition of D-glucose (D-Glc) gave no inhibition. HP binding to neuraminidase-treated lymphocytes was also investigated quantitatively by means of 125I-labeled HP. The number of HP molecules bound per HP-positive cell was approximately 3 X 10(5) and the apparent association constant for the binding of HP to its cellular receptors was approximately 8 X 10(7) 1/mol. No binding of HP to untreated lymphocytes could be recorded in these experiments.

Animals↗
PubMed1985

Aspects of the mechanisms of action of benzydamine.

Benzydamine shows some properties that are common with other nonsteroidal antiinflammatory drugs (NSAIDs) but displays also properties which are different from those of other NSAIDs. It inhibits prostaglandin and thromboxane biosynthesis at high concentrations, which however can be reached by topical application of the drug. It has no inhibiting effect on amino-acid decarboxylases, which are inhibited by various NSAIDs. Benzydamine has no effect on sulphydryl-group reactivity, contrary to most NSAIDs. It inhibits platelet aggregation and the inhibition of the collagen-induced aggregation appears to be rather selective with respect to other NSAIDs. It displays a stabilizing effect on erythrocyte membranes which appears related to its high affinity for membranes in general, and it inhibits the respiratory burst of stimulated human monocytes and granule enzyme release by human neutrophils.

Animals↗