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Biomedical subjects

L Milne

Publications and source records attributed to L Milne.

31 records · Page 2Linked to original sources
PubMed1995

Significance of systemic endotoxaemia in inflammatory bowel disease.

Quantitative and qualitative disturbances in faecal flora suggest a role for enteric bacteria and their products in the pathogenesis of inflammatory bowel disease (IBD). This study investigated the hypothesis that systemically circulating endotoxins are of pathogenic significance in IBD by measuring antibody, cytokine, and acute phase protein responses. Systemic endotoxaemia was found in 88% patients with ulcerative colitis (n = 25) and 94% with Crohn's disease (n = 31) during clinical relapse. Systemic endotoxaemia correlated positively with anatomic extent and clinical activity of ulcerative colitis. Circulating tumour necrosis factor (TNF) was detected in 40% of patients with ulcerative colitis and 45% with Crohn's disease. Plasma TNF concentrations correlated with clinical and laboratory measures of disease activity and were associated with a surgical outcome to the disease episode. Plasma soluble TNF receptor p55 concentration correlated positively with disease activity and endotoxin core antibody concentrations. Plasma IgG endotoxin core antibody concentrations were significantly increased in patients with Crohn's disease and correlated with systemic endotoxaemia. The presence of systemic endotoxaemia, its correlation with disease activity, disease extent, and endotoxin core antibody concentration and the detection of circulating TNF and soluble TNF receptors all support a pathogenic role for endotoxins in IBD.

Adolescent↗
PubMed1995

Isolation, characterization and structure of a new allenic polyine antibiotic produced by fungus LL-07F275.

Antibiotic 07F275 (1), produced by submerged fermentations of fungal culture LL-07F275, was isolated and characterized despite its inherent instability. Its UV spectrum was identical with that of nemotin, a member of the allenic polyacetylene family, but a molecular weight of 218 daltons indicated a new compound. Structure 1 was determined on the basis of spectroscopic evidence, particularly NMR. Since 1 is a thirteen carbon-containing allenic diyne, it is closely related to mycomycin.

Alkynes↗
PubMed1994

Calcium indicator dye Quin2 inhibits hydrogen peroxide-induced DNA strand break formation via chelation of iron.

Exposure of HeLa cells to H2O2 at 4 degrees C caused DNA strand breakage which was prevented by the metal chelator 1,10-phenanthroline, but not by neocuproine. This is believed to indicate the participation of iron, rather than copper, in the formation of reactive hydroxyl radicals (.OH) from H2O2. The calcium indicator dye Quin2 also prevented H2O2-induced DNA fragmentation. The inhibition of oxidant-induced DNA fragmentation at 37 degrees C by Quin2 is often presented as evidence for the involvement of Ca(2+)-dependent endonucleases in damage. However, our finding that Quin2 inhibits DNA fragmentation at 4 degrees C led us to investigate the possibility that Quin2 may also inhibit DNA damage via its effects on metal-dependent .OH formation. Using ESR spin trapping techniques and in vitro DNA oxidation measurements, we found that the binding of Fe by Quin2 does not prevent .OH formation, but inhibits DNA damage. This is believed to reflect the prevention of iron ion binding to DNA by Quin2, directing .OH generation to the bulk solution, thereby preventing damage. The Cu-Quin2 complex was found to be a poor catalyst of both .OH formation and in vitro DNA damage. These findings suggest that the frequently reported protective effect of Quin2 toward DNA in cells exposed to oxidants may be due to the chelation of metal ions rather than the prevention of Ca(2+)-dependent endonuclease activation.

Aminoquinolines↗
PubMed1994

Effect of dietary lipids and endocrine changes on polyunsaturated fatty acids in phospholipids of pancreas and brown adipose tissue of obese and lean rats.

Obese (fa/fa) rats fed on control diet have lower proportions of linoleic acid (18:2n-6) and/or arachidonic acid (20:4n6) in IBAT and pancreas phospholipids compared with lean (Fa/-) rats. Lower stearic acid (18:0) to oleic acid (18:1n-9) mean ratios in fa/fa compared with Fa/- suggest enhanced delta 9-desaturase activity in the former. 18:2/20:4 mean ratios in pancreas, but not IBAT, are indicative of a reduced delta 6-desaturase activity in fa/fa rats. Absolute amounts of phospholipids (mg/unit tissue wt) were 2-fold greater in IBAT of fa/fa compared with Fa/- rats, irrespective of their diet. This was reflected in greater absolute amounts of 18:2n-6 and 20:4n-6 only in HSO and HTO fa/fa groups, but not in the control group. Adrenalectomy (Adx) or T3 treatment also modified phospholipid fatty acid composition of IBAT and pancreas phospholipids in animals fed on the control diet with fa/fa rats more sensitive to endocrine induced changes. In fa/fa rats T3 treatment increased docosahexaenoic acid (22:6n-3) in IBAT of both phenotypes compared with the control, but this effect was evident only in fa/fa and not Fa/- pancreas. T3 treatment also increased docosapentaenoic acid (22:5n-3) in IBAT from, both phenotypes, but no 22:5n-3 was evident in the pancreatic tissue of these animals. ADX also increased 22:6n-3 in the IBAT of fa/fa (Fa/- values were less than 1%) but not in the pancreas of fa/fa or Fa/-. ADX modified the relative proportions of 18:0 to 18:1 and 18:2 to 20:4 in IBAT and pancreas of fa/fa in a way that indicated decreased delta 9-desaturase and increased delta 6-desaturase activities; these effects tended toward normal again in pancreas of fa/fa rats on corticosterone replacement (CST).

Adipose Tissue, Brown↗
PubMed1993

Effects of glutathione and chelating agents on copper-mediated DNA oxidation: pro-oxidant and antioxidant properties of glutathione.

The exposure of DNA to H2O2 in the presence of Cu(II) and a reducing agent is known to result in the induction of a variety of oxidative lesions, including DNA strand breaks and base modifications. Since the reducing agent glutathione occurs in cell nuclei at relatively high concentrations, and copper exists in nuclei associated with chromatin, the present study was undertaken to evaluate the ability of GSH to promote copper-mediated free radical damage to DNA. When compared with ascorbate, GSH was found to be inefficient in the promotion of damage to DNA. Parallel ESR spin trapping measurements indicated that GSH inhibits free radical formation by copper ions in the presence of H2O2, ascorbate, and DNA. The protective effect of GSH is attributed to its stabilization of copper in the +1 oxidation state, thereby compromising its ability to participate in free radical generating reactions. Consequently, it is suggested that the GSH in cell nuclei serves to prevent, rather than promote, copper-dependent damage to DNA. In contrast, in the presence of 1,10-phenanthroline, GSH stimulated free radical formation and DNA damage. This is attributed to the failure of GSH to remove copper(I) from 1,10-phenanthroline. Therefore, under these conditions, GSH serves primarily to redox cycle the reactive 1,10-phenanthroline-copper complex.

Ascorbic Acid↗
PubMed1991

Regulation of polyunsaturated fatty acid metabolism in tissue phospholipids of obese (fa/fa) and lean (Fa/-) Zucker rats. 1. Effect of dietary lipids on cardiac tissue.

The present investigation addressed three questions: (i) Does the obese syndrome alter the fatty acid composition of cardiac tissue and membrane phospholipids in obese (fa/fa) rats? (ii) Are changes, if they occur, similar to those reported for tissues of the genetically obese (ob/ob) mouse? (iii) Can cardiac tissue phospholipids and their component fatty acids be modified by dietary lipids and if so does this occur to the same extent in both fa/fa and lean (Fa/-) rats? Proportions of polyunsaturated fatty acids (PUFA) in cardiac total phospholipids of fa/fa rats differed significantly from those of Fa/- rats and from those reported for ob/ob mice. Increased 18:2n-6 and decreased 20:4n-6 and 22:6n-3 in fa/fa rats indicated impaired PUFA metabolism, possibly reduced delta 6 and/or delta 5 desaturase activity, compared with Fa/- rats. No differences in hepatic delta 6 and delta 5 desaturase activity between fa/fa and Fa/- were found but enhanced activity of delta 9 desaturase activity in fa/fa as compared to Fa/- was evident. Inclusion of sunflower oil (SO) or triolein (TO) at 5% and 20% by weight in the diet elicited marked changes in the fatty acyl composition of cardiac phospholipids in both fa/fa and Fa/- rats when compared with animals fed the control Oxoid diet alone. Supplementation with triolein was most effective, reducing 18:2n-6 and increasing 20:4n-6 proportions in fa/fa rats so that they resembled those in Fa/- rats fed the control Oxoid diet. The type of fat rather than the amount of its dietary intake appears to be the main determinant of the observed changes in phospholipid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Herpes simplex virus, Candida albicans and mouth ulcers in neutropenic patients with non-haematological malignancy.

Mouth ulcers are a frequent cause of morbidity in patients rendered neutropenic as a result of chemotherapy. We report here a series of 28 such patients from whom swabs were taken for viral isolation and mycological culture. In 13 patients, herpes simplex virus (type I) was isolated and in 17 patients Candida albicans was cultured. Both organisms were isolated in 9 patients. Our results suggest that both a viral and fungal element may be important in the aetiology of oral ulceration and that antiviral and antifungal agents may each have a role in the prophylaxis and treatment of such patients.

Agranulocytosis↗
PubMed1982

Clinical evaluation of a low lint surgical sponge.

To evaluate a new low lint, nonwoven surgical sponge material, a prospective, stratified, randomized, single blind study of 232 patients was carried out. Patients studied underwent thoracic, upper abdominal or lower abdominal operations. The new material, in the form of laparotomy pads and sponges, was compared with cotton gauze. Safety of the material was evaluated by a battery of biochemical and hematologic tests. No clinically significant differences were seen. Effectiveness was evaluated by measuring fluid absorption. The new material was significantly more effective than cotton gauze in both configurations studied. Since this article was completed, the sponge material has been refabricated into laparotomy pads which are appreciably softer and more comformable than the study pads. The newest revision has been cleared by the Food and Drug Administration for clinical use.

Abdomen↗
PubMed1980

Plasma concentration and metabolism of phenoperidine in man.

The plasma concentrations of phenoperidine were measured in five patients during general anaesthesia. The concentration of the drug decreased rapidly between 2 and 40 min and then declined more slowly. Detectable concentrations of phenoperidine were present in plasma for at least 3 h. In the five patients, the distribution half-life of the drug ranged from 3.19 to 14.23 min and the elimination half-life from 47.31 to 162.30 min. Unchanged phenoperidine and two identified metabolites (pethidine and norpethidine) were present in urine.

Adjuvants, Anesthesia↗
PubMedDate not supplied

Do diets work?

Explore the source record for details and available documents.

Diet, Reducing↗