Search PubMed⌕ Search

Biomedical subjects

G Morgan

Publications and source records attributed to G Morgan.

At least 127 records · Page 7Linked to original sources
PubMed1997

An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs.

The IARC convened a Working Group of experts in Lyon, France, on April 2-8, 1997 to evaluate the cancer-preventive activity of four nonsteroidal anti-inflammatory drugs (aspirin, sulindac, piroxicam, and indomethacin). Epidemiological observational studies of aspirin that differed in design, location, population, and motivating hypothesis have consistently shown that regular use lowers the risk for colorectal cancer by up to 50%; however, the one randomized trial did not show protection by aspirin. Definite evidence of chemopreventive activity normally requires data from appropriately designed randomized trials. The strength of the scientific evidence that aspirin prevents colorectal cancer in humans was thus considered to be limited. In animal models, there was sufficient evidence that aspirin prevented against cancer. Aspirin and aspirin-like drugs may have an important adverse side effects, the most frequent of which are gastrointestinal disturbances ranging in severity from dyspepsia to peptic ulcer. Given the remaining uncertainties in the preventive effect and the risk of adverse side effects, detailed consideration of the total benefits and of toxicity will be required before widespread use of aspirin for the prevention of colorectal cancer can be recommended. Sulindac shows promise in reducing the number and size of adenomatous polyps in patients with familial adenomatous polyposis. Further research is required, however, to determine whether and to what extent the risk for colorectal cancer in such patients is reduced. In people without familial adenomatous polyposis, there is inadequate evidence that sulindac has cancer-preventive activity. Fewer data were available on piroxicam and indomethacin than on aspirin and sulindac. Although these drugs consistently prevent colorectal cancers in experimental animal models, the evidence that they prevent colorectal cancer in humans was considered to be inadequate. The results of the meeting, including recommendations for future research, will be published as Volume 1 of the IARC Handbooks of Cancer Prevention.

Animals↗
PubMed1997

Characterization of a recombinant Onchocerca volvulus antigen (Ov33) produced in yeast.

A yeast (Saccharomyces cerevisiae) expression system has been adapted to produce reagent quantities of a major Onchocerca antigen, Ov33. Using a pool of monoclonal antibodies produced against third-stage larvae, a cDNA library constructed from adult O. volvulus worms was screened. Twenty-seven cDNAs were isolated, two of which had sequence homology to Ov33, a putative aspartyl protease inhibitor, which is the immunodominant antigen of O. volvulus. These cDNAs were expressed at high levels intracellularly or through the secretory pathway of S. cerevisiae. Localization studies using antisera produced against purified recombinant protein demonstrated that Ov33 is a very abundant parasite protein present in the hypodermis, muscle, and uterus of female worms, as well as in embryonic microfilariae. The soluble recombinant protein secreted by yeast (C71) demonstrated inhibitory activity against the aspartyl protease pepsin. Antibodies to the recombinant protein-mediated leukocyte adherence to and killing of skin microfilariae. The sensitivity of a diagnostic test using recombinant Ov33 was evaluated using sera from 441 patients. The mean sensitivities for the two recombinant constructs, C27 and C71, were 82.2% and 85.4%, respectively. The combined sensitivity using both recombinant proteins was 94%.

Animals↗
PubMed1997

Immune stimulation by syphilis and malaria in HIV-2-infected and uninfected villagers in West Africa.

Co-infections such as Mycobacterium tuberculosis (TB) and Pneumocystis pneumonia may affect the progress of HIV infection and speed the onset of death. As malaria and syphilis are both endemic in West Africa we examined their effects on HIV-2 infection, for these may also accelerate the progress of disease. A community-based case-control study was undertaken in a rural village in Guinea-Bissau, West Africa. One hundred and fifty asymptomatic subjects seropositive for HIV-2 and 154 age- and sex-matched controls were enrolled. Venous blood samples taken into EDTA were stained within six hours of collection with CD4 and CD8 monoclonal antibodies and processed by Q-Prep machine in the field. The stained cells were then transported on ice by road and analysed by FACS-can at the base laboratory in The Gambia within a week. The mean CD4% was significantly lower and geometric mean neopterin and beta 2-microglobulin levels were significantly higher in the HIV-2-infected subjects than in the controls (P < 0.01 for all cases versus all controls). The mean CD4% was lower and beta 2-microglobulin level was higher in both HIV-2 and control subjects with active or past syphilis when compared with subjects with no syphilis; however, syphilis did not have a marked effect on plasma neopterin level. Malaria infection raised neopterin levels, but had little effect on CD4%. Overall multiple regression analysis allowing for HIV-2 infection and other variables showed that syphilis lowered CD4% (P = 0.01) and raised beta 2-microglobulin levels (P = 0.05) and malaria raised neopterin levels (P = 0.05). The conclusions are that HIV-2 infection is associated with lower CD4% and higher neopterin and beta 2-microglobulin levels than controls, and co-infection with syphilis is associated with a further lowering of CD4%, suggesting a worse suppression of the immune system. Co-infection with malaria is associated with a modest immune disturbance.

Adult↗
PubMed1996

Mutation analysis in CD40 ligand deficiency leading to X-linked hypogammaglobulinemia with hyper IgM syndrome.

Mutations in the gene encoding CD40 ligand have been shown to be the cause of X-linked hypogammaglobulinemia with hyper IgM (HIGM1). We have used the technique of single strand conformational polymorphism (SSCP) analysis to screen for mutations in this gene in affected boys from nineteen unrelated families. Sixteen novel mutations were identified in patients, comprising six patients with single base substitutions, two patients with single base insertions, six patients with deletions ranging from one to seven bases and two patients with large deletions at the 5' end of the gene. These mutations were distributed throughout the gene SSCP band shifts and/or alterations in restriction enzyme digestion sites could be used for unambiguous determination of carrier status in at-risk female relatives of most of the affected boys and, in some cases, prenatal diagnosis also can be offered.

Agammaglobulinemia↗
PubMed1996

Effects of interleukin 6 administration on platelets and haemopoietic progenitor cells in peripheral blood.

Platelet numbers and circulating haemopoietic progenitor cells were examined in 12 patients with advanced malignancies who were receiving recombinant human interleukin-6 (rhIL-6) as part of an investigation of its thrombopoietic effects. Patients received recombinant glycosylated IL-6 by daily subcutaneous injection for 7 consecutive days in doses of 1, 3 or 10 micrograms/kg/day. Platelet numbers increased reaching a peak on days 12-15 with a mean on day 15 of 198.1% of pre-treatment values. This was accompanied by a significant fall in the mean platelet volume (mean decrease of 10.6%, P = 0.0044). No significant correlation was seen between the IL-6 dose and the change in platelet number. No significant differences were observed between pre- and post-treatment levels of circulating erythroid burst-forming units (E-BFU) and granulocyte macrophage colony-forming units (GM-CFU) but a small significant increase was seen in circulating primitive progenitor cells measured in a plastic-adherent (P delta) assay (P = 0.025). As positive controls, a group of patients treated with cyclophosphamide/G-CSF showed significant increases in GM-CFU (P = 0.018), E-BFU (P = 0.018) and P delta progenitors (P = 0.028). These data suggest that the thrombopoietic effects of IL-6 are mediated at a relatively late stage via effects on megakaryocyte differentiation, with a relatively small effect on circulating haemopoietic progenitors.

Adult↗
PubMed1996

Calcium transport and the localisation of calbindin-D9k in the ruminant placenta during the second half of pregnancy.

In late pregnancy the sheep fetus requires 3 g of calcium per day, all of which must be transported across the trophoblast epithelium of the placenta. Such high levels of calcium transport across other epithelia are normally associated with the presence of calbindin-D9 or -28k. Our immunocytochemical results show that ovine, bovine and caprine interplacentomal trophoblast have high levels of calbindin-D9k, about eight to ten times more than in the placentomal region. The protein is detectable only in the uninucleate trophoblast cells in sheep and goat, the frequent binucleate cells show none. The calbindin-D9k is also present in the maternal glandular epithelium but not the surface epithelium of the uterus. The cellular distribution of the calbindin-D9k immunoreactivity suggests a soluble protein homogenously distributed through cytosol and nucleoplasm but absent from all organelles and intercellular spaces. In contrast, the uterine milk protein(s) are localised in Golgi cisternae and secretory vesicles in gland cells and in apical small endocytic vesicles and lysosomes in the uninucleate trophectodermal cells. The distribution of calbindin-D9k supports the concept that it mediates the high calcium flux by facilitated diffusion and not via any vesicular, membrane-bounded system.

Animals↗
PubMed1996

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Abdominal Neoplasms↗