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Biomedical subjects

I Clark

Publications and source records attributed to I Clark.

At least 19 recordsLinked to original sources
PubMed1991

Actinomycin D upregulates lipopolysaccharide induction of macrophage procoagulant expression and tumour necrosis factor-alpha production.

The antitumour antibiotic actinomycin D (Act D) and the aminosugar D-galactosamine both enhance the sensitivity of animals to bacterial lipopolysaccharide (LPS). Lipopolysaccharide stimulates macrophage membrane-bound procoagulant activity (MPCA) and tumour necrosis factor-alpha (TNF-alpha) production in vitro. We investigated the effects of LPS combined with either Act D or D-galactosamine on procoagulant and TNF-alpha production in vitro. Actinomycin D directly induced procoagulant on the malignant monocytoid cell line WEHI 265, and synergized with LPS to enhance MPCA on both WEHI 265 cells and thioglycollate-induced peritoneal exudate macrophages. In the presence of Act D, exudate macrophages expressed procoagulant in response to concentrations of LPS 100,000-fold lower than normally required. Pulsing experiments demonstrated that LPS primed these cells within 4 h to respond to Act D, whereas 4 h priming with Act D inhibited subsequent procoagulant induction by LPS. Although its effects on TNF-alpha production were less intense, low levels of Act D more than doubled TNF-alpha produced by LPS-stimulated exudate macrophages. Procoagulant expression and TNF-alpha production were not always co-ordinately expressed; interferon-gamma (IFN-gamma) synergized with LPS to enhance both responses but when IFN-gamma was combined with Act D only procoagulant was upregulated. D-galactosamine failed to affect these macrophage responses. Results indicate different in vivo mechanisms of enhancement of LPS toxicity by these two agents.

Animals↗
PubMed1991

Immunoblotting and culture positive endocarditis.

Serum samples from patients with endocarditis due to Streptococcus mutans, Streptococcus pneumoniae, Streptococcus agalactiae, Streptococcus lactis and a "nutritionally" variant streptococcus were immunoblotted against antigenic extracts from all five species. In S mutans endocarditis there was an endocarditis specific pattern of IgM against bands of 220, 200, and 190 kilodaltons. In S pneumoniae IgM against antibody of a molecular weight greater than 150 kilodaltons was specific to endocarditis. In S agalactiae IgM against bands at 82, 71, and 66-67 kilodaltons was endocarditis specific. In S lactis endocarditis specific IgM was present against antigenic bands at 105, 66, 61 and 58 kilodaltons. With the "nutritionally" variant streptococcus it was impossible to distinguish between cases of endocarditis and controls.

Antibodies, Bacterial↗
PubMed1991

Activities of a cancellous bone-cell-stimulating substance.

A bone-cell-stimulating substance (BCSS) that initiates appositional bone formation in intact rats was examined for its effects on DNA and collagen synthesis in tibial and calvarial organ cultures of 17-day-old embryonic chicks. BCSS stimulated collagen synthesis in both types of bone. BCSS stimulated DNA synthesis in tibiae but inhibited synthesis in calvaria from the same chicks. Insulinlike growth factor, transforming growth factor-beta, platelet-derived growth factor, and fetal bovine serum also affected DNA synthesis differently in calvaria and tibiae. BCSS was able to modify some of the effects of these growth factors on DNA.

Animals↗
PubMed1990

Characterization of the antibody response in Corynebacterium jeikeium septicaemias.

Corynebacterium jeikeium causes septicaemia in neutropenic patients usually after colonizing intravenous lines. This paper reports the results of immunoblotting sera from 14 patients with a C. jeikeium septicaemia. Recovery from the septicaemia was associated with production of both IgM and IgG against antigenic bands of 50, 52 and 110 kDa. Antibody against the 110 kDa band was present in controls but the antibody against the 50 and 52 kDa was specific to those patients who had on-going or previous C. jeikeium infection. A case of C. jeikeium endocarditis is also presented and here recovery was associated with seroconversion to the 50 and 52 kDa bands.

Antibodies, Bacterial↗
PubMed1990

The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs.

The SIN3 gene (also known as SDI1) is a negative regulator of the yeast HO gene. Mutations in SIN3 suppress the requirement for the SWI5 activator for expression of the yeast HO gene and change the normal asymmetric pattern of HO expression in mother and daughter cells. Furthermore, the in vitro DNA-binding activity of several DNA-binding proteins is reduced in extracts prepared from sin3 mutants. We have cloned the SIN3 gene and determined that a haploid strain with a SIN3 gene disruption is viable. We determined the sequence of the SIN3 gene, which is predicted to encode a 175-kDa polypeptide with four paired amphipathic helix motifs. These motifs have been identified in the myc family of helix-loop-helix DNA-binding proteins and in the TPR family of regulatory proteins. The SIN3 transcript was mapped, and it was determined that the SIN3 transcript was absent in stationary-phase cells. Immunofluorescence microscopy with anti-SIN3 antibody demonstrated that SIN3 protein was present in nuclei. A comparison of restriction map and sequence data revealed that SIN3 is the same as regulatory genes UME4 and RPD1.

Amino Acid Sequence↗
PubMed1989

Diagnosing endocarditis with the cloned 112 kDa antigen of Enterococcus faecalis.

A new indirect ELISA is presented for the diagnosis of enterococcal endocarditis. It is based on the cloning of Enterococcus faecalis DNA into lambda gt11. The library was screened by antisera from three cases of E. faecalis endocarditis. Three positive clones were found, all of which cross-reacted with the 112 kDa antigen of E. faecalis. One of these was taken and lysogenised into E. coli Y1089 to produce a fusion protein of 125 kDa. This IPTG dependent protein was purified by affinity chromatography and used in an indirect ELISA. The test differentiated between five cases of enterococcal endocarditis (IgG ELISA optical density greater than 0.8) and patients with endocarditis due to staphylococci (IgG ELISA optical density less than 0.243) and other streptococci (IgG ELISA optical density less than 0.656). Patients with a simple E. faecalis septicaemia had a maximum IgG ELISA optical density of 0.636. The only major cross-reaction occurred in patients with Streptococcus bovis endocarditis.

Antibodies, Bacterial↗
PubMed1989

Immunoblot fingerprinting Aspergillus fumigatus.

A new technique for typing Aspergillus fumigatus is presented. This is based on immunoblot fingerprinting each isolate against a rabbit hyperimmune antiserum raised against A. fumigatus NCTC 2109. All isolates were typable and reproducibility for the 16 antigenic bands which formed the basis of the system was excellent. Discrimination was better than silver staining and revealed 11 types among the 21 isolates from eight patients with an aspergilloma. Each aspergilloma could be due to either a single or multiple types.

Animals↗
PubMed1988

Candida and AIDS: evidence for protective antibody.

Clinical observation and animal models of candidosis suggest that, although T lymphocytes are important in preventing superficial candidosis, defence against systemic candidosis depends upon humoral immunity. An antibody response to the immunodominant 47 kD antigen of Candida albicans is invariably associated with recovery. The presence of this antibody in patients with chronic mucocutaneous candidosis and the acquired immunodeficiency syndrome (AIDS) could account for the rarity of disseminated candidal infection in these conditions. Polyclonal B cell activation may be responsible for the frequency with which this antibody is produced in AIDS. Antibody to the 47 kD antigen could be useful in the treatment and prevention of systemic candidosis, though not in the superficial candidosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Bone-cell-stimulating substance.

An acid-pepsin extract of ground cancellous calf bone contains a bone-cell-stimulating substance (BCSS) that is active in the intact rat and in bone cultures. A single injection of a suspension of BCSS adjacent to the radius-ulna complex of a rat significantly increased appositional bone formation in a dose-dependent manner. The pattern of new bone deposition differed from that caused by nonspecific irritants. A suspension or water-soluble extract of BCSS significantly increased DNA and collagen synthesis in organ cultures of diaphyseal pieces of 17-day-old fetal chick tibiae. Whether or not BCSS is different from any of the other bone-derived growth factors has not been established.

Animals↗
PubMed1987

Activation of the yeast HO gene by release from multiple negative controls.

Transcription of the yeast HO gene requires five genes, SWI 1, 2, 3, 4, 5. We present evidence that some SWI products activate HO by antagonizing negative regulatory activities encoded by the SIN genes. sin- mutants (defining six genes) were identified because they express HO in the absence of particular SWI products. We argue that SWI5 activates HO by antagonizing SIN3 and that SWI4 activates HO by antagonizing SIN6. HO is expressed in sin3- daughter cells, hence we infer that the SIN3 product represses HO in wild-type daughter cells and that SWI5 and SIN3 are responsible for the cell-lineage-dependent expression of HO. HO is transcribed only when all types of repression are absent: in mother cells, where SWI5 antagonizes SIN3; in late G1, when SWI4 antagonizes SIN6; and in a or alpha cells, where a1-alpha 2 repression is absent.

Chromosome Deletion↗
PubMed1987

Effect of transplanted osteogenic sarcoma on urinary RNA catabolites.

The usefulness of urinary RNA catabolites as markers for the early detection of a transplantable rat tumor and for the completeness of its resection was evaluated. The lack of correlation between tumor growth or size and the time of appearance of the elevated catabolites precludes their use for the early detection of cancer in this model. Complete removal of the tumor restored the elevated levels to normal but, if regrowth occurred, the elevated levels persisted, suggesting their possible use in monitoring the effectiveness of surgery. The data suggest that increased excretion of RNA catabolites is derived primarily from host tissue.

Animals↗
PubMed1986

Evaluation of the computing aspects of automatic analysers.

Modern automatic analysers are making increasing use of microprocessor technology, which is difficult for the user, or even computer scientists, to evaluate. This paper offers some practical advice for the prospective purchaser on how to assess the capabilities and limitations of the computer hardware and software provided in such instruments, and considers some of the problems of interfacing an analyser to a laboratory computer system.

Autoanalysis↗
PubMed1985

Aluminium salts accelerate peroxidation of membrane lipids stimulated by iron salts.

Aluminium salts do not themselves stimulate peroxidation of ox-brain phospholipid liposomes, but they greatly accelerate the peroxidation induced by iron(II) salts at acidic pH values. This effect of Al(III) is not seen at pH 7.4, perhaps because Al(III) salts form insoluble complexes at this pH in aqueous solution. Peroxidation of liposomes in the presence of Al(III) and Fe(II) salts is inhibited by the chelating agent desferrioxamine, and by EDTA and diethylenetriaminepentaacetic acid at concentrations greater than those of Fe(II) salt. Aluminium salts slightly stimulate the peroxidation of peroxide-depleted linolenic acid micelles, but they do not accelerate the peroxidation induced by addition of iron(II) salts to the micelles at acidic pH. Aluminium salts accelerate the peroxidation observed when human erythrocytes are treated with hydrogen peroxide at pH 7.4. Desferrioxamine decreases the peroxidation. We suggest that Al(III) ions produce an alteration in membrane structure that facilitates lipid peroxidation, and that the increased formation of fluorescent age pigments in the nervous system of patients exposed to toxic amounts of Al(III) may be related to this phenomenon. The ability of desferal to bind both iron (III) and aluminium(III) salts and to inhibit lipid peroxidation makes it an especially useful chelating agent in the treatment of 'aluminium overload'.

Aluminum↗
PubMed1985

Iron exclusion from aflatoxin B1-induced hepatocellular carcinoma in rats.

Mixed-cell hepatocellular adenocarcinomas, induced by aflatoxin B1 (AFB1) in weanling rats, were allowed to develop for 18 months; age- and sex-matched controls were maintained. After 18 months, treated and control rats were administered iron dextran (ID), intraperitoneally (i.p.) as Nonemic. No gross or microscopic lesions were observed in control animals, while hepatic tumors were observed grossly in all AFB1-treated rats. Areas of apparently normal tissue, in histologic sections from control animals and in non-tumor sites of sections from AFB1-treated animals, were deeply stained for iron, both in endothelial cells and in hepatocytes, as visualized by Perls iron stain. Varying degrees of exclusion of stainable iron material were noted in histologic sections of lesions from AFB1-treated rats, as were alterations in endothelial cell staining characteristics. Iron staining clearly demonstrates the presence of varying cell populations within the induced mixed cell hepatocellular adenocarcinoma.

Adenocarcinoma↗