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Biomedical subjects

M Kenney

Publications and source records attributed to M Kenney.

At least 19 recordsLinked to original sources

Association of a common interferon regulatory factor 5 (IRF5) variant with increased risk of systemic lupus erythematosus (SLE).

Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors that control the transactivation of type I interferon system-related genes, as well as the expression of several other genes involved in immune response, cell signalling, cell cycle control and apoptosis. Two recent studies reported a significant association between the IRF5/rs2004640 T allele and systemic lupus erythematosus (SLE). The purpose of this study was to determine whether the reported rs2004640 T allele association could be replicated in our independent SLE case-control sample. We genotyped DNA samples from 370 white SLE-affected female subjects and 462 white healthy female controls using the TaqMan Assay-on-Demand for rs2004640, and performed a case-control genetic association analysis. Frequency of the rs2004640 T allele was significantly higher in cases than in controls (56.5% vs. 50%; P= 0.008). The odds ratio for T allele carriers was 1.68 (95% CI: 1.20 - 2.34; P= 0.003). Our results in an independent case-control sample confirm the robust association of the IRF5/rs2004640 T allele with SLE risk, and further support the relevance of the type I interferon system in the pathogenesis of SLE and autoimmunity.

Adolescent↗

Preconditioning of human smooth muscle cells via cyclopentenone prostaglandins protects against toxic effects of oxidized low-density lipoprotein.

Human vascular smooth muscle cells (SMC) exhibit upregulation of inducible heat shock protein 70 (Hsp70), upon exposure to oxidized low-density lipoproteins (LDL(ox)). The presence of Hsp70 is thought to protect the cell against the toxic effects of the modified lipoprotein. In order to test this hypothesis, Hsp70 in SMC was upregulated by exposure to Delta(12) prostaglandin J(2) (Delta(12)PGJ(2)) before cells were exposed to LDL(ox). Hsp70 levels were measured after exposure to Delta(12)PGJ(2) and before exposure to LDL(ox). Cell protection was monitored after LDL(ox) exposure by determination of cell toxicity measured by cell lactate dehydrogenase (LDH) release into the medium. Cells treated with Delta(12)PGJ(2) exhibited a 23-fold increase in Hsp70 levels and 56% lower LDH activity release after exposure to LDL(ox) when compared to cells that were not pretreated with Delta(12)PGJ(2). In addition, cells pretreated with prostaglandins that did not induce Hsp70 did not exhibit increased tolerance against the toxic effects of LDL(ox). The results support a protective role for Hsp70 against the toxic effects of LDL(ox) and hint at the potential for the use of small molecules for the prevention of deleterious effects of LDL(ox) through heat shock protein upregulation.

Cyclopentanes↗

Induction of heat shock protein 70 by herbimycin A and cyclopentenone prostaglandins in smooth muscle cells.

This study characterizes Hsp70 induction in human smooth muscle cells (SMC) by herbimycin A and cyclopentenone prostaglandins. The magnitude of Hsp70 induction by cyclopentenone prostaglandins was 8- to 10-fold higher than induction by herbimycin A. Hsp70 induction by delta12PGJ2 was first observed at 10 microM, rose to 4000-5000 ng/mL within one log unit and a maximum response was not observed; concentrations of delta12PGJ2 higher than 30 microM were toxic to the cells. A maximum response with herbimycin A (500 ng/mL) was reached at 0.05 microM and maintained to 1 microM without toxicity. Both, delta12PGJ2 and herbimycin A, were inhibited by dithiothreitol (DTT, 100 microM) at lower concentrations and became less sensitive to inhibition at higher concentrations. Hsp70 induction after incubation of SMC with delta12PGJ2 followed by addition of herbimycin A was significantly higher than Hsp70 induction after incubation with herbimycin A followed by addition of delta12PGJ2. When cells were incubated with [3H]-PGJ2, followed by protein denaturation, substantial radioactivity remained protein-bound suggesting that the prostaglandin must be covalently bound. Covalent binding was largely insensitive to DTT. Maximal Hsp70 induction was observed after 5 minutes of exposure of the cells to herbimycin A followed by a 20 hour recovery period in agent-free medium. Cells required 3-4 hours of exposure to delta12PGJ2 followed by a 20 hour recovery period in order to see high Hsp70 induction. Binding of the heat shock factor (HSF) to the heat shock element (HSE) in the presence of herbimycin A or delta12PGJ2, and the effects of DTT, mirrored the results of Hsp70 induction. The results suggest that probable differences between the 2 agents are at the level of the signal transduction prior to HSF activation.

Anti-Bacterial Agents↗

Immobilization of acrylamide-modified oligonucleotides by co-polymerization.

A flexible chemistry for solid phase attachment of oligonucleotides is described. Oligonucleotides bearing 5'-terminal acrylamide modifications efficiently co-polymerize with acrylamide monomers to form thermally stable DNA-containing polyacrylamide co-polymers. Co-polymerization attachment is specific for the terminal acrylamide group. Stable probe-containing layers are easily fabricated on supports bearing exposed acrylic groups, including plastic microtiter plates and silanized glass. Attachment can be accomplished using standard polyacrylamide gel recipes and polymerization techniques. Supports having a high surface density of hybridizable oligonucleotide (approximately 200 fmol/mm2) can be produced.

Acrylamides↗

Mutation typing using electrophoresis and gel-immobilized Acrydite probes.

A new electrophoresis technology for hybridization-based sequence detection and mutation typing is described. Intrinsic to this approach is copolymerization of specially modified oligonucleotide probes directly into polyacrylamide gels. Electrophoresis of single-stranded samples through gels containing specific immobilized probes results in hybridization-mediated capture of complementary targets. By increasing gel temperature or including denaturants in the buffer, the method can be used to type single-nucleotide polymorphisms. The method can easily be adapted to type mutations in PCR-amplified samples. Acrydite gel technology will also be useful for many other applications, including hybridization-based diagnostics, analysis of gene expression and purification of nucleic acids from biological samples.

DNA Mutational Analysis↗

Determining research priorities in pediatric nursing: a Delphi study.

A two-round Delphi study was performed in Pediatric Nursing at a large midwestern teaching hospital. The purpose of the study was to identify research priorities for the Pediatric Research committee for future projects. The initial survey was sent to all pediatric nursing staff. Sixty-two staff (19%) responded to the first round. Forty-five separate research topics/themes of interest were identified. The second round survey was sent to the 62 staff who responded to Round 1. Forty-eight staff (76%) responded. Participants were given a list of the 45 topics identified in Round 1, and asked to identify their top five priorities. Results were analyzed by unit and by Division. The identified priorities for the Division are described here.

Clinical Nursing Research↗

Photodynamic therapy (PDT) of the ciliary body with silicon naphthalocyanine (SINc) in rabbits.

BACKGROUND AND OBJECTIVE: To investigate silicone naphthalocyanine (SINc; 0.5 mg/kg) for photodynamic therapy (PDT) of the ciliary body in pigmented rabbits. STUDY DESIGN/MATERIALS AND METHODS: SINc was dissolved in canola oil by heating, emulsified with Tween-80, and given by ear vein. Pharmacokinetics were studied in frozen sections by fluorescence microscopy using a CCD camera-based, low light detection system with digital image processing at 1 hr and 24 hr (12 rabbits, 24 eyes total). A Ti:Sapphire laser delivered light at 770 nm by contact fiberoptic (1,000 microns; 80 mW/cm2;20,40 and 80 J/cm2). Controls (5 rabbits), received laser light at 770 nm without SINc. For comparison, eyes received continuous wave Nd:YAG laser by fiberoptic contact (0.8-1.2 J). RESULTS: Localization studies showed intravascular distribution shifting to a ciliary body distribution at 24 hr. PDT at 1 hr and 24 hr postinjection showed a more selective destruction of the ciliary body at 24 hr. Ciliary processes treated at 24 hr showed infarction and marked edema with sparing of iris. Tissue thermal damage was minimal in PDT controls. Eyes treated with the Nd:YAG laser exhibited full-thickness thermal necrosis of iris, ciliary processes, and a fibrinous iridocyclitis. In contrast, eyes treated by PDT were quiet with thrombosis of superficial blood vessels. CONCLUSION: Tissue photon penetration is good at 770 nm and thermal effects from the exciting laser alone were minimal. The ciliary processes of pigmented rabbits exhibit a selective retention of SINc and on that basis can be selectively destroyed with a minimum on thermal damage to nontarget tissues.

Aluminum Oxide↗

Characterization of the subunit isoforms of duck salt gland Na/K adenosine triphosphatase.

The N-terminal sequences of the alpha and beta subunits from the Na/K-ATPase of duck salt gland have been determined by automated Edman degradation chemistry. These sequences were compared to sequences previously reported for Na/K-ATPase subunits from other sources in order to determine the subunit isoform composition of the salt gland enzyme. The comparisons indicate that the duck salt gland enzyme is composed of an alpha-1 subunit and a beta-1 subunit. This subunit isoform composition is consistent with the involvement of this enzyme in sodium excretion as Na/K-ATPases in other tissues involved in sodium excretion also have this subunit isoform composition.

Amino Acid Sequence↗

Infection of man with Trichuris vulpis, the whipworm of dogs.

A gravid female Trichuris was found in histopathologic sections of an appendix in a post-mortem examination, and a posterior extremity of a male Trichuris was recovered from the unsectioned portion of the same appendix. These parasites were identified as T. vulpis, the whipworm of dogs.

Animals↗

Two cases of enteric myiasis in man. Pseudomyiasis and true intestinal myiasis.

Dipterous larvae were found in the appendices from two postmortem examinations. The single maggot in the first case was not immediately identified in the sections. However, when the posterior end of the larva was recovered from the unsectioned portion of the appendix, it was identified as a maggot of the genus Sarcophaga. The first case was believed to be a case of "pseudomyiasis,+ i.e., the accidental entrapment of a swallowed larva passing through the digestive tract. In the second case, the appendix contained numerous larvae with great variation in sizes and stages of development of the mouth hooks, pharyngeal sclerites, and spiracular breathing plates. Such development was considered to have occurred within the intestinal tract, which indicated that this was a case of true intestinal myiasis.

Aged↗

Laboratory diagnosis of autoinfection in strongyloidiasis.

Among 10,072 examinations of concentrated stools, Strongyloides stercoralis rhabditiform larvae were found in 93, and filariform larvae in four. In two of the four cases harboring filariform larvae, subsequent stools revealed only rhabditiform larvae, but filariform larvae continued to be found in the stools and sputum of the other two cases. It was concluded that only two of the cases were true autoinfections, and the other two apparent cases resulted from prolonged storage of unrefrigerated stools in the hospital ward. The importance of distinguishing true autoinfections from a free-living Strongyloides life cycle in stools is stressed.

Animals↗