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G M Galbraith

Publications and source records attributed to G M Galbraith.

51 records · Page 3Linked to original sources
PubMed1980

The human materno-foetal relationship in malaria: I. Identification of pigment and parasites in the placenta.

To facilitate investigations of the consequences of malarial infection during human pregnancy, several methods for the recognition of pigment and parasites in the placenta were evaluated. Pigment was visualized in infected blood smears and placental tissue using both white light and modified fluorescence microscopy. However, the characteristic pigment dots observed with fluorescent light were also apparent in unstained cryostat and deparaffinized placental sections, and following reaction with immunohistological reagents. Intact parasites were recognized immunohistologically in placental sections and blood smears using rabbit antisera to Plasmodium falciparum and P. berghei. Using these procedures, numerous erythrocytes containing parasites associated with small pigment dots were seen in intervillous spaces in heavily infected placentae. In these organs, larger irregular pigment aggregates were present within maternal cells which were shown to be monocytes by esterase staining. Pigment was also observed in the cytoplasm of the trophoblast and not infrequently in the mesenchymal stroma, but no intact parasites were observed within chorionic villi. These simple and sensitive methods thus confirm placental localization of parasites and pigment. Furthermore, the finding of pigment in all Gambian placentae examined, of which seven were thought initially to be uninfected, indicates that malaria may complicate pregnancy more frequently than hiterto anticipated.

Esterases↗
PubMed1980

The human materno-foetal relationship in malaria. II. Histological, ultrastructural and immunopathological studies of the placenta.

Histological and ultrastructural studies of four placentae heavily infectd with Plasmodium falciparum revealed large intervillous accumulations of erythrocytes containing parasites together with monocytes which had ingested pigment. These appearances were associated with focal syncytial necrosis, loss of syncytial microvilli and proliferation of cytotrophoblastic cells. In addition, marked irregular thickening of trophoblastic basement membranes and protrusion of tongue-like projections of syncytiotrophoblast into the basement membrane were observed. In six other placentae which contained scanty amounts of pigment but no parasites, representing past or inactive infection, no large collections of monocytes or abnormalities of trophoblast were apparent but basement membrane thickening was evident. Immunohistological studies revealed no significant differences between placentae positive for parasites and those containing pigment only, although the amount of certain immunoproteins and clotting factors was clearly increased above normal. These findings establish that P. falciparum infection in the placenta may result in substantial damage although lesions within the villus are rare. Furthermore, previous infection, although adequately controlled, may leave a heritage of pigment deposition, basement membrane thickening and immunopathological lesions. These results may thus account for both the high frequency of intra-uterine growth retardation and the rarity of congenital malaria in the presence of P. falciparum malaria.

Female↗
PubMed1980

Transferrin binding to peripheral blood lymphocytes activated by phytohemagglutinin involves a specific receptor. Ligand interaction.

Immunohistological studies have indicated that membrane sites binding transferrin are present upon activated human peripheral blood lymphocytes. In this study, we have investigated transferrin uptake in human lymphocytes exposed to phytohemagglutinin (PHA), by quantitative radiobinding and immunofluorescence in parallel. In stimulated lymphocytes, binding was maximal after a 30-min incubation, being greatest at 37 degrees C, and greater at 22 degrees C than at 4 degrees C. Although some shedding and endocytosis of transferrin occurred at 22 degrees and 37 degrees C, these factors, and resulting synthesis of new sites, did not affect measurement of binding which was found to be saturable, reversible, and specific for transferrin (K(a) 0.5-2.5 x 10(8) M(-1)). Binding was greater after a 48-h exposure to PHA than after 24 h, and was maximal at 66 h. Sequential Scatchard analysis revealed no significant elevation in affinity of interaction. However, although the total number of receptors increased, the proportion of cells in which binding of ligand was detected immunohistologically increased in parallel, and after appropriate correction, the cellular density of receptors remained relatively constant throughout (60,000-80,000 sites/cell). Increments in binding during the culture period were thus due predominantly to expansion of a population of cells bearing receptors. Similar differences in binding were apparent upon comparison of cells cultured in different doses of PHA, and in unstimulated cells binding was negligible. Transferrin receptors appear, therefore, to be readily detectable only upon lymphocytes that have been activated.

Dose-Response Relationship, Drug↗
PubMed1980

Demonstration of transferrin receptors on human placental trophoblast.

It has been postulated that the transplacental passage of maternal iron to the developing fetus requires binding of maternal transferrin to the trophoblast. We have therefore examined the ability of the human placenta to bind transferrin in vitro. Transferrin was demonstrated on trophoblast of human chorionic villi by immunohistologic methods. Moreover, after removal of transferrin bound in vivo by treatment of tissue with chaotropic solution or phosphate-buffered saline, freshly added transferrin was shown to bind in vitro in the same characteristic distribution. These findings suggest that placental iron transport is initiated by uptake of maternal transferrin iron to specific trophoblast binding sites.

Albumins↗
PubMed1980

Metabolic and cytoskeletal modulation of transferrin receptor mobility in mitogen-activated human lymphocytes.

The transferrin receptors which appear on mitogen-activated human peripheral blood lymphocytes were found by the use of immunofluorescence techniques to display temperature-dependent patching and capping reactions upon binding of transferrin. Lateral mobility of ligand-occupied membrane sites was accompanied by both shedding and endocytosis of receptor-transferrin complexes. In the presence of sodium azide or the microfilament inhibitor cytochalasin B, cap formation and shedding were markedly inhibited. In contrast, endocytosis of patched receptor-ligand complexes was inhibited by azide and microtubule inhibitors, including colchicine, vinblastine and vincristine. Co-capping experiments performed to elucidate further the alterations in membrane configuration involved in these reactions failed to reveal any topographical relationship between transferrin receptors and lectin-binding sites in these cells. These studied indicate that temperature-dependent mobility of transferrin receptors upon mitogen-activated peripheral blood lymphocytes is dependent upon the integrity of the cytoskeletal system and metabolic function of the cell.

Binding Sites↗
PubMed1979

Trophoblast transferrin and transferrin receptors in the host--parasite relationship of human pregnancy.

Transferrin and specific transferrin receptors are demonstrated on the microvillous surface of syncytiotrophoblast in human immature and term placentae by immuno histological techniques with the use of light and electron microscopy. That the distribution of transferrin is limited to the materno-foetal interface supports the hypothesis that binding of maternal transferrin to trophoblast receptors is involved in the process of iron transport to the foetus. Parallel studies with baboon placentae demonstrate the presence of trophoblast receptors which bind both baboon and human transferrin, thereby putting forward an experimental model which might be used to test the biological significance of placental transferrin receptors in primates. In addition, investigation of a large number of human cell lines shows that many transformed cells, but no normal cells (such as blood lymphocytes) or cells from primary culture (such as neonatal foreskin fibroblasts), possess the ability to bind transferrin to their membranes. These findings suggest that transferrin receptors may play important biological roles in addition to that of iron transport from mother to foetus. One such role could be the limitation of iron in intervillous spaces, thus depriving iron-requiring microorganisms of iron, hence serving as a non-specific factor of resistance for placentae. Another role for foetal transferrin receptors on trophoblasts could be to bind maternal transferrin at the materno-foetal interface, thus frustrating maternal immunosurveillance. This is similar to a mechahism used by schistosomes in the host-parasite relation where host proteins are bound by the parasite to escape immunological recognition. The presence of transferrin receptors on transformed cells suggests that this mechanism might also be employed by tumour cells. Finally, in view of previous studies which show that transferrin is required by stimulated lymphocytes to pass from the G1 to the S phase of cellular replication, it is proposed that trophoblast transferrin receptors could limit the amount of transferrin in intervillous spaces and thus impede the proliferation and possible cytotoxicity of maternal activated lymphocytes at the materno-foetal interface.

Female↗
PubMed1978

Detection of H-Y antigen by fluorescence microscopy.

A rapid and reproducible fluorescence microscopic technique has been devised to demonstrate H-Y antigen on membranes of human peripheral blood mononuclear cells. In 11 male subjects, 20 to 32% of mononuclear cells were positive for H-Y antigen, whereas less than 1% of such cells from 6 female donors were seen to be stained.

Animals↗
PubMed1978

A new allele of human alpha1-antitrypsin: PiNhampton.

A new allele of alpha1AT is described. By isoelectric focusing, the microheterogeneous pattern of the variant was similar to but more cathodal than that of Pi N. This allele has therefore been tentatively designated PiNhampton(Nham). Further examination revealed that the minor bands of Nham are indistinguishable from the major bands of Z by isoelectric focusing, and a careful family study was necessary to clearly define the proband's phenotype. Pi Nham was found in association with M1, S, and Z, but to date its possession is not apparently related to clinical disorders or reduced serum levels of alpha1AT.

Adult↗
PubMedDate not supplied

Effect of protein kinase C inhibitors on calcium ionophore-induced arachidonic acid mobilization in human leukocytes.

Arachidonic acid mobilization in human polymorphonuclear leukocytes stimulated with calcium ionophore A23187 was amplified by synthetic diacylglycerol and, to a much lesser extent, by phorbol ester. The effect was synergistic and dependent upon influx of calcium ions. Thin layer chromatographic analysis of phospholipids of stimulated cells revealed a loss of arachidonic acid associated with phosphatidylinositol and phosphatidylcholine. The synergistic response was unaffected by treatment of cells with two inhibitors of protein kinase C, namely, polymyxin B and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. Moreover, both agents consistently augmented the cellular response to A23187 alone. These findings suggest that A23187-induced arachidonic acid mobilization in leukocytes is independent of protein kinase C activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

Immunological studies of transferrin and transferrin receptors of human placental trophoblast.

In primate pregnancy, fetal iron is derived from maternal transferrin; however, the mechanisms by which iron is taken up by the human placenta have not yet been established. In the present study, transferrin was demonstrated on the microvillous surface of human trophoblast in immunohistological studies of 130 mature and immature placentae from both normal and abnormal pregnancies. Similar results were found for baboon placentae. Upon short-term culture of placental tissue, the amount of trophoblast transferrin decreased and no incorporation of 14C lysine into transferrin could be detected by radioimmunoelectrophoresis. Thus this transferrin apparently was not synthesized by the placenta. When transferrin was removed from cryostat sections of placenta by treatment with chaotropic agents, subsequently added transferrin bound in an identical distribution. The specificity of this reaction was confirmed by the lack of binding of other serum proteins and by displacement procedures in which trophoblast transferrin was shown to be dislodged by transferrin added in vitro. These findings suggest that placental iron transport is predicated by binding of transferrin to specific receptors on trophoblast.

Animals↗
PubMedDate not supplied

Health-care workers and latex allergy.

Latex hypersensitivity can pose a threat to anyone, but health-care providers are among the high-risk groups for developing latex hypersensitivity. Latex hypersensitivity likely results from health-care workers' increased use of gloves following implementation of universal precautions. It is also believed that the antigenic load of latex gloves causes an increase in latex hypersensitivity resulting from massive production of gloves. Although there are many studies on the prevalence of latex hypersensitivity among health-care workers, there appear to be discrepancies, which may affect the different apparent prevalence. Testing for latex hypersensitivity raises another problem. Latex allergens cannot be identified specifically; therefore, there is no standard test or testing solution that can identify hypersensitive persons. Although latex glove hypersensitivity was first identified in the late 1970s, there remain many uncertainties associated with it; as a result, there is a growing concern among health-care providers. The authors offer several precautions to avoid the development of latex hypersensitivity.

Female↗
PubMedDate not supplied

Tumor necrosis factor alpha gene expression in human monocytic THP-1 cells exposed to beryllium.

Chronic beryllium disease, which results from occupational exposure to particulate beryllium, is characterized by the development of lung granulomas and progressive pulmonary fibrosis. Increased production of proinflammatory cytokines (e.g., tumor necrosis factor alpha and interleukin-1 beta) by pulmonary alveolar macrophages occurs in many chronic fibrotic lung diseases and is thought to contribute to the disease process. The purpose of the present study was to investigate cytokine production by human monocytic cells exposed to beryllium in vitro. The results indicated that such cells respond to beryllium ions in the presence of fluoride by accumulation of messenger ribonucleic acid for both tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that inhaled beryllium may directly stimulate the production of these cytokines by alveolar macrophages in vitro.

Beryllium↗
PubMedDate not supplied

Inhibition of lymphocyte activation by antisera to embryonic antigens shared with human placental trophoblast.

In order to further examine the inhibition of lymphocyte activation reported with conventional antisera to human trophoblast membranes, we studied their effects on cells stimulated by antigen in mixed lymphocyte culture (MLC) and by the mitogen phytohemagglutinin. The results were compared with the effects of antisera known to recognize intrinsic membrane determinants on activated T cells (DR antigens and placental alkaline phosphatase) and with those of antisera to normal human serum components such as transferrin which may bind to the activated lymphocyte membrane. The results indicated that antibodies to placental alkaline phosphatase, which constitutes the predominant specificity of conventional trophoblast membrane antisera, caused inhibition both of MLC response and, to a lesser extent, of activation induced by mitogen. Similar inhibition was obtained with antisera to human DR antigens, while antisera to normal human serum and transferrin were not suppressive. These findings, together with time course studies and immunocytochemical studies of the homologous antigens, suggest that these antisera mediate their inhibitory effects in part through binding to antigens which appear on cells as they undergo activation.

Alkaline Phosphatase↗