PubMed Health⌕ Search

Biomedical subjects

G Conn

Publications and source records attributed to G Conn.

15 recordsLinked to original sources

Do British travel agents provide adequate health advice for travellers?

Travel-related illness is a burden for primary care, with more than two million travellers consulting a general practitioner each year. The annual cost of travel-related illness in the United Kingdom is 11 million Pounds. Travel agents are in a unique position to influence this burden as the most common and most serious problems are preventable with simple advice and/or immunisation. This study, using covert researchers, suggests this potential is not being fully utilised.

Female↗

Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor.

Hepatocyte growth factor (HGF) has been shown to function as a potent mitogen for a variety of cells, transducing its signal through the c-met tyrosine kinase receptor. Ciliary neurotrophic factor (CNTF) is a cytokine that has been shown to promote survival of motor neurons. We show here that c-met mRNA is present in the embryonic rat spinal cord. Peak expression of c-met (at E14) coincides with the period of naturally occurring cell death in motor neurons, suggesting a possible role of HGF in the regulation of this process. Utilizing a neuron-enriched culture system, we established that HGF, like CNTF, stimulates choline acetyltransferase (CAT) activity in motor neurons. When co-administered to motor neuron cultures, saturating concentrations of HGF and CNTF produced a synergistic increase in CAT levels. We show that this synergy reflects enhanced motor neuron survival. Exposure of motor neuron cultures to the cytostatic agent vincristine markedly decreased CAT levels; co-treatment with HGF and CNTF (but not either factor alone) restored CAT activity to control levels. Our findings indicate that HGF is a survival factor for motor neurons, that it acts synergistically with CNTF, and that HGF and CNTF can together be neuroprotective in the face of vincristine toxicity.

Animals↗

Purification and characterization of a naturally occurring vascular endothelial growth factor.placenta growth factor heterodimer.

Vascular endothelial growth factor (VEGF) is a potent and selective mitogen for endothelial cells that is angiogenic in vivo and induced by hypoxia. A homologous protein, placenta growth factor (PlGF), is also reported to be mitogenic for endothelial cells in culture. The rat GS-9L glioma cell line produces not only VEGF homodimers but also PlGF homodimers and a novel heterodimer composed of VEGF and PlGF subunits. All three dimeric forms were purified to apparent homogeneity, and their structures and mitogenic activities were compared. VEGF.PlGF heterodimers are vascular endothelial cell mitogens nearly as potent as VEGF homodimers. Therefore, some of the biological activities attributed to VEGF homodimers might be mediated by VEGF.PlGF heterodimers. In contrast, pure PlGF homodimers are mitogenic for endothelial cells only at high, possibly non-physiologic concentrations; thus the biological relevance of their mitogenic activity for these cells is not obvious. However, the existence of not only homodimers but also heterodimers clearly extends the similarity between the VEGF/PlGF and the homologous platelet-derived growth factor systems.

Amino Acid Sequence↗

Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line.

A growth factor that is mitogenic for vascular endothelial cells, with an ED50 of approximately 1 ng/ml, has been purified 170,000-fold to apparent homogeneity from tissue culture medium conditioned by a rat glioma-derived cell line. The pure protein is a 46-kDa dimer composed of two subunits of equivalent mass as established by comparison of migration in SDS/polyacrylamide gels with and without prior reduction. This glioma-derived growth factor is a glycoprotein and is not mitogenic for BALB/c 3T3 fibroblasts, properties that further distinguish it from other well-characterized vascular endothelial cell mitogens. In contrast to acidic and basic fibroblast growth factors and to platelet-derived endothelial cell growth factor, which have no secretory leader sequences and might only be released by leakage from damaged cells, the glycoprotein nature of this mitogen implies that it is processed through the glycosylating secretory pathway. This secretable growth factor could, therefore, be readily available in the extracellular space under normal physiological conditions in vivo to promote vascular endothelial cell proliferation associated with blood-vessel growth and maintenance.

Amino Acids↗

Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor.

Glioma-derived vascular endothelial cell growth factor (GD-VEGF) is a 46-kDa dimeric glycoprotein mitogen with apparently greater specificity for vascular endothelial cells than the well-characterized fibroblast growth factors. The GD-VEGF cDNA sequence encodes a 190-amino acid residue subunit that is converted, by removal of an amino-terminal hydrophobic secretory leader sequence, to the mature 164-residue subunit characterized by direct amino acid sequencing. The GD-VEGF homodimeric subunit is homologous to the platelet-derived growth factor A and B chains and its oncogene homologue v-sis.

Amino Acid Sequence↗

Extracellular matrix heparan sulfate proteoglycans modulate the mitogenic capacity of acidic fibroblast growth factor.

Confluent cultures of human endothelial cells deposit into extracellular matrix (ECM) distinct heparan sulfate proteoglycans (HSPG) which modulate acidic fibroblast growth factor's (aFGF) ability to stimulate human endothelial cell mitogenic capacity. Extracellular matrix 35S-HSPG were isolated from cultures metabolically labelled with Na235SO4 by DEAE-Sepharose, Sepharose CL-4B, and aFGF-Affi-Gel 15 column chromatography and identified by resistance to chondroitinase ABC and sensitivity to nitrous acid. Fifty to sixty percent of the 35S-HSPG deposited into ECM do not bind aFGF. The bound 35S-HSGP (40-50% of the total counts applied) eluted from the aFGF-Affi-Gel column after the addition of buffer containing 2 M NaCl. aFGF-binding and aFGF-nonbinding 35S-HSPG were individually pooled and further purified by Sepharose CL-4B column chromatography. 35S-HSPG which bind aFGF, designated HSPGP, were 100-fold superior to heparin in augmenting the mitogenic efficacy of aFGF in sparse proliferating cultures. In contrast, however, 35S-HSPG, which did not bind aFGF, designated HSPG1, inhibited aFGF-stimulated proliferation in both sparse and subconfluent endothelial cell cultures. The majority of the biological activity of both aFGF-potentiating HSPGP and aFGF-inhibitory HSPG1 was contained in the glycosaminoglycan chains released by alkaline borohydride treatment of intact HSPGP or HSPG1, respectively. 3H-Core protein derived from HSPGP or HSPG1 contained only minor biological activity. The ability of heparitinase or heparinase (Flavobacterium heparinum) to abolish biological activity differed, depending upon the HSPG tested, also suggested that these are two distinct HSPGs.

Cell Division↗

The complete amino acid sequence of human brain-derived acidic fibroblast growth factor.

Acidic fibroblast growth factor is a potent mitogen for a variety of cells in culture, including vascular endothelial cells, and is angiogenic in vivo. The complete amino acid sequence of human brain-derived acidic fibroblast growth factor has been determined from amino terminal sequence analysis and carboxypeptidase A digestion of the whole protein and sequence analyses of peptides generated by tryptic, Staphylococcus aureus V8 protease and cyanogen bromide cleavages. A potential Asn-Gly-Ser glycosylation sequence is present in the human protein. The complete amino acid sequence is compared to that of the equivalent protein purified from bovine brain.

Amino Acid Sequence↗

Human brain-derived acidic and basic fibroblast growth factors: amino terminal sequences and specific mitogenic activities.

Extended amino terminal sequence determinations, made on both acidic and basic fibroblast growth factors from human brain, showed extensive homology with each other and with their respective bovine counterparts. Both human growth factors in the presence of heparin have equivalent specific mitogenic activities on human umbilical vein endothelial cells in culture whereas in the absence of heparin, the acidic mitogen is less than 1% as active as the basic growth factor.

Amino Acid Sequence↗

Isolated plasma membranes regulate neurotransmitter expression and facilitate effects of a soluble brain cholinergic factor.

The choice of which transmitter will be expressed by a neuron is influenced by diffusible differentiating factors produced by a variety of nonneuronal cells. In this study we show that human, bovine, and rat brains contain a soluble heparin-binding factor that stimulates cholinergic and peptidergic expression. We also show that neuronal contact with other cell membranes influences neurotransmitter development and acts synergistically with the effects of the soluble brain factor. Exposure of cultured sympathetic neurons to purified plasma membranes derived either from cultured Schwann cells or from cultured sympathetic neurons promoted expression of choline acetyltransferase (CAT), a cholinergic trait, and of substance P (SP). CAT activity and SP were also stimulated by a 50-kDa soluble protein that was purified 14,000-fold from human, calf, and rat brain by heparin-Sepharose affinity chromatography. CAT activity after concurrent treatment with plasma membranes and the soluble factor far exceeded the sum of the enzyme activities after the individual treatments, suggesting that membrane molecules and the factor facilitated each other. Thus, cell-surface molecules, which have been shown previously to influence neuronal morphogenesis and neurite elongation, may also help determine the transmitter phenotype of the neuron. Moreover, cell-surface molecules may modulate the effects of diffusible differentiating factors.

Animals↗

Glycosaminoglycan production in cultures of early and late passage human endothelial cells: the influence of an anionic endothelial cell growth factor and the extracellular matrix.

An endothelial cell (EC) growth factor isolated from bovine brain stimulates in vitro growth of human umbilical vein endothelial cells, and permits long term serial propagation. In the presence of increasing concentrations of EC growth factor, confluent cultures of early (CPDL less than or equal to 20) and late (CPDL greater than 20) passage human endothelial cells exhibit an increased incorporation of 3H-glucosamine and Na235SO4 into the glycosaminoglycans (GAG), hyaluronic acid, chondroitin, chondroitin-4-sulfate, dermatan-4-sulfate, and chondroitin-6-sulfate. An increase in both labelled sulfated and nonsulfated GAG was observed in the cytosol, membrane, secreted and extracellular matrix fractions. In contrast, endothelial cells grown in the presence of EC growth factor contained decreased amounts of labelled heparan sulfate than cells grown without EC growth factor. Confluent cultures of early passage cells had significantly more labelled GAG but significantly less heparan sulfate than cultures of late passage cells on a per cell basis. Extracellular matrix from early passage cells contained about two- to seven-fold more labelled GAG than extracellular matrix from late passage cells, but only about half as much labelled heparan sulfate. Cell adhesion was enhanced when cells were grown in the presence of EC growth factor as compared to adhesion of cells grown without EC growth factor. Conversely, trypsin-mediated detachment of cells grown in the presence of growth factor was inhibited as compared to detachment of cells grown in medium without EC growth factor. The composition of the extracellular matrix influenced incorporation of labelled GAG into extracellular matrix. Early passage cells grown to confluence on a matrix from late passage cells incorporated significantly less labelled GAG into extracellular matrix than when grown to confluence on matrix from early passage cells. Incorporation of labelled GAG into extracellular matrix was significantly higher when late passage cells were grown on a matrix from early passage endothelial cells than when grown on matrix from late passage cells. We conclude that EC growth factor selectively stimulates incorporation of isotopic precursors into GAG in cultures of early and late passage endothelial cells but inhibits incorporation of radiolabel into heparan sulfate; early passage cells contain more GAG but less heparan sulfate than late passage cells, extracellular matrix controls the amount of GAG and heparan sulfate incorporated into matrix.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗

Peri-incisional mezlocillin versus rectal-metronidazole for wound infection prophylaxis.

One hundred and forty patients who underwent appendicectomy were included in a prospective randomized trial to compare the ability of preoperative rectal metronidazole and peri-incisional mezlocillin to prevent wound infection following appendicectomy. The results show that bactericidal local tissue levels of mezlocillin were uniformly achieved using the peri-incisional technique. The wound infection rate for the metronidazole group was found to be 15.9% and did not significantly differ from the wound infection rate when mezlocillin was used (10.4%). Peri-incisional mezlocillin therefore appears to be a viable prophylactic technique against wound infection following appendicectomy and may offer a cheaper alternative to intravenous intra-operative metronidazole administration in cases when pre-operative metronidazole suppositories have been omitted. The peri-incisional mezlocillin technique is also suitable for routine prophylaxis against wound infection following appendicectomy.

Adolescent↗

The isolation and purification of two anionic endothelial cell growth factors from human brain.

Two anionic polypeptides which stimulate the proliferation of human umbilical vein endothelial cells have been isolated and purified to homogeneity from human brain using heparin affinity chromatography. The molecular weights of the polypeptides are 18,500 and 19,300; the isoelectric point for both polypeptides is at pH 5.2. The purified polypeptides differed in their ability to stimulate human endothelial cell growth. The half maximal activities observed for the 18.5 and 19.3 kilodalton polypeptides were at concentrations of 10.0 ng/ml and 0.9 ng/ml respectively.

Brain Chemistry↗

Build a gentle ramp.

Explore the source record for details and available documents.

Architecture↗