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Biomedical subjects

G Gallagher

Publications and source records attributed to G Gallagher.

At least 91 records · Page 5Linked to original sources
PubMed1988

Responses of human B-cells to recombinant lymphokines.

The effects of recombinant or purified cytokines on the growth and differentiation of human B-cells from a variety of sources were evaluated. The results suggest that IL-1, BCGF and BSF-2 have either "growth-factor" or "differentiation-factor" activity and that only IL-2 has both these functions. In addition, evidence is presented that the two forms of human IL-1 affect B-cell growth differently. Finally, the separation of human normal and leukaemic B-cells into subsets defined by their buoyant cell density, is described.

B-Lymphocytes↗
PubMed1987

Maturation signals for human B cells. Use of the MTT assay and EBV-transformed cell lines to define signals which promote cell growth or immunoglobulin secretion.

There are now several relatively well-defined signals that promote B-cell growth and maturation, usually termed 'growth' and 'differentiation' factors (e.g., IL-1, IL-2, BCGF, BSF-1 (IL-4) and BSF-2). In addition, much work has been carried out using continuous cell lines to examine the effects of these two classes of material. Using two different assays to enumerate cell growth and the ELISA to quantify Ig secretion, we would like to emphasize the importance of determining the final cell number when investigating so-called 'differentiation factors', particularly when continuous cell lines are the targets. The results presented here show that materials which promote DNA synthesis in B-cell lines (e.g., IL-1, BCGF) will also cause an increase in Ig secreted, suggesting that they can also promote Ig synthesis. However, when we used the MTT assay to quantitate cell numbers at the end of the assay and then calculated the Ig secreted per cell, only BSF-2 caused an increase in Ig secreted per cell. These results illustrate the importance of determining the final cell number when using continuous cell lines to investigate the actions of materials which modulate human B cell function and suggest that the MTT assay is a simple way of doing this.

Antibody-Producing Cells↗
PubMed1987

Dopamine agonists related to 3-allyl-6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzaz epi ne-7, 8-diol. 6-Position modifications.

The N-allyl derivative (SK&F 85174) of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol (SK&F 82526) retains the DA-1 agonist potency of the latter compound but unlike the parent also shows substantial DA-2 agonist activity. In a previous study of N-substituted benzazepines these combined agonist effects were shown to be uniquely associated with the N-allyl group. A continuation of this research has examined dependency of combined DA-2/DA-1 agonist activities on 6-position modification with the specific objective of developing an agonist with maximum effectiveness and potency at the DA-2 receptor subtype. DA-2 agonist activity was measured in a rabbit ear artery assay, and DA-1 agonist activity was determined in an adenylate cyclase assay. Replacing chloro with bromo retains the activity pattern and the potency of the chloro compound; replacement with a hydrogen causes a decrease of both DA-1 and DA-2 receptor activating potency. Introduction of a 6-methyl group causes loss of DA-2 agonist activity and reduction in DA-1 agonist potency. Substitution with a 6-fluoro provides the best balance of DA-2 and DA-1 agonist activities; this compound was moderately potent in both assays.

Adenylyl Cyclases↗
PubMed1987

Separate but complementary roles for the two forms of interleukin 1 in the growth of transformed human B lymphoblasts.

Epstein-Barr virus (EBV)-transformed human B cells were seeded at densities below their capacity for autostimulatory growth and the effects of interleukin 1-alpha (IL-1-alpha), interleukin 1-beta (IL-1-beta) and B-cell growth factor (BCGF) were studied. When added separately, IL-1-alpha was able to support the growth of EBV-transformed B cells, as was BCGF. In contrast, IL-1-beta was unable to support the growth of these cells but was able to synergize with IL-1-alpha to promote cell growth. Further, the actions of BCGF and IL-1-alpha were seen to be synergistic, while those of BCGF and IL-1-beta were not. The secretion of immunoglobulin was not affected by these reagents. These findings suggest separate, but complementary roles for the two forms of human IL-1 in B-cell growth.

B-Lymphocytes↗
PubMed1987

Structure and expression of a tandem gene pair in Leishmania donovani that encodes a protein structurally homologous to eucaryotic cation-transporting ATPases.

An oligonucleotide probe was used to clone a cation-transporting ATPase gene from the genome of Leishmania donovani. The nucleotide sequence of the gene contained a 2,922-base-pair open reading frame that was predicted to encode a 107,406-dalton protein composed of 974 amino acids. The predicted L. donovani protein contained all the structural and functional domains expected to be present in a cation-transporting ATPase of the aspartyl phosphate class. The nucleotide sequence encoding the ATPase gene was duplicated in tandem in the parasite genome. Partial sequenation of the second member of the tandem repeat, which lay 2 kilobase pairs downstream of the ATPase gene, indicated that it was either identical to the first gene or very closely related to it. RNA homologous to either the ATPase gene or its adjacent relative was 5 kilobases in size and was approximately equally abundant in both promastigote and amastigote forms of the organism.

Adenosine Triphosphatases↗
PubMed1987

The human bladder carcinoma line T-24 secretes a human B-cell differentiation factor.

The effect of a B-cell differentiation factor (BCDF) found in the supernatant of the human bladder carcinoma cell line T-24 (T-24.BCDF) was assessed using the human lymphoblastoid line CESS (Muraguchi et al., 1981) and TPA-stimulated human B-CLL B cells. This T-24.BCDF was shown to cause both these cell types to secrete immunoglobulin, and therefore indicates that culture supernatants from this bladder carcinoma line contain a potent differentiation factor for human B cells.

Cell Line↗
PubMed1987

T-24.B-cell differentiation factor induces immunoglobulin secretion in human B cells without prior cell replication.

Stimulation of B lymphocytes from B-cell chronic lymphocytic leukaemia (B-CLL) with 12-0-tetradecanoylphorbol-13-acetate (TPA) has shown that these cells are capable of differentiation (Totterman, Nilsson & Sundstrom, 1980). Increases in the expression of different class II MHC antigens (Guy et al., 1983, 1986) and responsiveness to growth factors (Kabelitz et al., 1985; Suzuki, Butler & Cooper, 1985) have been studied. Supernatant from the human bladder carcinoma line T-24 contains a B-cell differentiation factor (BCDF) able to induce immunoglobulin secretion from CESS cells. We investigated the induction of proliferation and immunoglobulin secretion in human B cells by studying the effects of this factor on B-CLL cells, in both the presence and absence of TPA. We report here that this material (termed T-24.BCDF) causes immunoglobulin secretion to be initiated in these cells, and that this is not accompanied by detectable DNA synthesis. These observations were extended to normal human B cells and demonstrate that human B cells can secrete immunoglobulin in the absence of clonal expansion.

B-Lymphocytes↗
PubMed1987

Effect of dopamine-related drugs on duodenal ulcer induced by cysteamine or propionitrile: prevention and aggravation may not be mediated by gastrointestinal secretory changes in the rat.

Dose- and time-response studies have been performed with dopamine agonists and antagonists using the cysteamine and propionitrile duodenal ulcer models in the rat. The experiments demonstrate that the chemically induced duodenal ulcer is prevented by bromocriptine, lergotrile and reduced by apomorphine or L-dopa. Aggravation of cysteamine-induced duodenal ulcer was seen especially after (-)-butaclamol, (-)-sulpiride, haloperidol and, less effectively, after other dopaminergic antagonists. The duodenal antiulcerogenic action of dopamine agonists was more prominent after chronic administration than after a single dose, whereas the opposite was found concerning the proulcerogenic effect of dopamine antagonists. In the chronic gastric fistula rat, both the antiulcerogens bromocriptine or lergotrile and the proulcerogens haloperidol, pimozide or (-)-N-(2-chlorethyl)-norapomorphine decreased the cysteamine- or propionitrile-induced gastric secretion. No correlation was apparent between the influence of these drugs on duodenal ulcer development and gastric and duodenal (pancreatic/biliary) secretions. In the chronic duodenal fistula rat, decreased acid content was measured in the proximal duodenum after haloperidol, and diminished duodenal pepsin exposure was recorded after bromocriptine. Furthermore, the aggravation by dopamine antagonists of experimental duodenal ulcer probably involves a peripheral component. The site of dopamine receptors and physiologic effects which modulate experimental duodenal ulcer remain to be identified, but their elucidation may prove to be an important element in the pathogenesis and treatment of duodenal ulcer.

Animals↗
PubMed1986

Syntheses and in vitro evaluation of 4-(2-aminoethyl)-2(3H)-indolones and related compounds as peripheral prejunctional dopamine receptor agonists.

A series of (beta-aminoethyl)indolones and related compounds was synthesized and evaluated in vitro as peripheral prejunctional dopaminergic agonists in the field-stimulated isolated perfused rabbit ear artery. 4-[2-(Di-n-propylamino)ethyl]-7-hydroxy-2(3H)-indolone was the most potent compound (ED50 = 2 +/- 0.3 nM) tested, while the related secondary amine 24 and the des-OH derivatives 28 and 34 were only slightly less potent. 4-Methoxybenzeneethanamine and 2-methyl-3-nitrophenylacetic acid were employed as starting materials for for the synthesis of the 4-(beta-aminoethyl)indolones. The ring-opened 3-acylamino analogues 46 and 47 were prepared via nitration of the phenethylamine 43 derived from 4-methoxyphenylacetic acid. The inactive isomeric indolones 38, 39, and 41 were derived from 4-nitrobenzeneethanamine and from indolone-6-acetic acid.

Animals↗
PubMed1986

Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogues of fenoldopam.

Certain 6-halo-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines were found to be potent D-1 dopamine agonists. The 1-(4-hydroxyphenyl) analogues did not have central nervous system activity because their high polarity inhibited entry into the brain. However, these compounds were potent renal vasodilators. Fenoldopam, the 6-chloro analogue, is an especially significant member of the series, and its synthesis, pharmacology, and clinical properties have been studied extensively. The 6-methyl and 6-iodo congeners were potent renal vasodilators, but nonpotent partial D-1 agonists as measured by stimulation of rat caudate adenylate cyclase. A possible rationalization suggests different receptor reserves for these activities. The 9-substituted benzazepines were either inactive or of low potency as dopamine agonists, while the N-methyl analogues had significant antagonist potency as measured by inhibition of dopamine stimulation of rat caudate adenylate cyclase.

Adenylyl Cyclases↗
PubMed1986

Human T-cell hybrids secreting lymphokines: effect of different parent cell clones of the human T-cell acute lymphoblastoid leukaemia line CCRF-CEM.

We have cloned a number of cell lines from the human T-lymphocyte acute lymphoblastoid leukaemia (ALL) line CCFR-CEM, and attempted to construct functionally active human T-lymphocyte hybrids with them. Functional hybrids were generated using only one particular clone, 3H6. The activities found in the supernatants of two of these hybrids, DB1G7 and DB2D10, are described. Supernatant from DB1G7 was found to suppress strongly the migration of normal human peripheral blood mononuclear cells, while that from DB2D10 was shown to inhibit the proliferative response of human T lymphocytes to both phytohaemagglutinin and concanavalin A. There was no cross-reactivity between the two supernatants, confirming the usefulness of the human T-lymphocyte hybrid technique in dissecting human T-lymphocyte function. The successful use of 3H6 is contrasted with the failure of another clone, 2H2, to permit the production of functional hybrids. Problems relating to the use of CCRF-CEM and its clones as parent cell lines in the production of human T-lymphocyte hybrids are discussed.

Cell Line↗
PubMed1985

4-[2-(Di-n-propylamino)ethyl]-2(3H)-indolone: a prejunctional dopamine receptor agonist.

4-[2-(Di-n-propylamino)ethyl]-2(3H)-indolone (1c) (SK&F 101468) is a potent and selective prejunctional dopamine receptor agonist. It caused a dose-related inhibition of the constrictor response to electrical stimulation in the isolated perfused rabbit ear artery (EC50 = 100 nM), and this response was antagonized by (S)-sulpiride (KB = 7 nM). Compound 1c did not stimulate or block dopamine-sensitive adenylate cyclase and did not produce stimulation of the central nervous system in rats. It was prepared from (2-methyl-3-nitrophenyl)acetic acid in a multistep sequence based on the Reissert indole synthesis.

Animals↗
PubMed1985

A histologic study of epithelial dysplasia in oral lichen planus.

One hundred cases of oral lichen planus were reviewed together with 100 nonspecific oral mucosal inflammatory lesions as a control group. The presence of dysplasia was noted, using well-established histologic criteria. Mild dysplasia was found in 57% of cases, moderate dysplasia in 9%, and severe dysplasia in 2% of cases. In the control group, mild dysplasia was observed in 32% of cases, moderate in 10%, and severe dysplasia was not present. It is suggested that, while mild or moderate dysplasia may not indicate precancerous potential, severe dysplasia in lichen planus may signify the development of a precancerous lesion.

Adult↗
PubMed1984

Human T-cell hybrids with HLA-restricted proliferative response to Epstein-Barr virus-infected B cells.

Human T-cell hybrids were constructed from an HGPRT-negative mutant of the acute lymphoblastoid leukaemia cell-line CEM and an uncloned population of T cells from donor SW (SW-T; partner cell) known to have a strong specificity for the autologous Epstein-Barr virus (EBV)-transformed B cell, SWEBV. The resulting hybrids, 1A9, 1D12 and 2C8, were shown not to be cytotoxic to SWEBV, nor did they have natural killer-like (NK) activity. However, when presented with the target SWEBV in a mixed lymphocyte reaction (MLR), all of the hybrids rapidly increased their rate of proliferation by up to a factor of seven. Hybrid 1D12 also produced interleukin-2-like material (IL2) under these conditions. The hybrids did not react with the autologous PHA-blasts (SWPHA), nor with various unrelated targets. When tested against a bank of EBV-transformed B-cell targets, it was observed that the human T-cell hybrids 1A9 and 2C8 responded only to those targets bearing the antigen HLA Bw35. This response could be blocked by treating the target with the monoclonal antibody W6/32, specific for a shared determinant of the HLA-A, -B and -C antigens. Similarly, the human T-cell hybrid 1D12 reacted only against those targets bearing the antigen HLA DrW2, and this activity could be blocked by the monoclonal antibody DA6.231, specific for a common region of the HLA-DR and SB antigens. Thus, human T-cell hybrids can be produced which exhibit HLA-restricted responses to antigenic stimulation.

Antigens, Surface↗
PubMed1983

Generation of human T-cell hybrids with the characteristics of human peripheral blood T-lymphocytes.

Using a selection system based on the two irreversible biochemical inhibitors, actinomycin-D and emetine hydrochloride, we have constructed human T-lymphocyte hybrids between the human T-cell line, Molt-4F, and mitogen-activated human lymphocytes. The cells were identified as true hybrids by their karyotype, differences in supernatant activities, responses to mitogen and membrane characteristics. These hybrid cells are stable in culture and express functions found in mature human T-lymphocytes.

Adult↗
PubMed1976

Synthesis of 1- and 2-substituted indazoles as anthelmintic agents.

Selective synthesis of 1- and 2-acyl-, alkoxycarbonyl-, and carbamoylindazoles are described. Spectroscopic data which were the basis for structural assignments are presented. These compounds, particularly methyl 2H-indazole-2-carboxylate and N-heptyl-N-methyl-2H-indazole-2-carboxamide, lack the spectrum of anthelmintic activity of the benzimidazole and benzotriazole anthelmintics to which they are structurally related.

Animals↗