Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor.

Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase metabolism of arachidonic acid that exert a broad range of physiologic activities, including modulation of inflammation, ovulation and arterial blood pressure. PGE2, a chief cyclooxygenase product, modulates blood pressure and fertility, although the specific G protein-coupled receptors mediating these effects remain poorly defined. To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-).

Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting.

Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that inhibits both the classical and the alternative pathways of complement activation. DAF has been studied extensively in humans under two clinical settings: when absent from the erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH) patients, who suffer from complement-mediated hemolytic anemia, and in transgenic pigs expressing human DAF, which have been developed to help overcome complement-mediated hyperacute rejection in xenotransplantation. Nevertheless, the exact role of DAF in regulating complement activation in vivo on the cell surface and the species specificity of this molecule remain to be fully characterized.

Sequence and analysis of the genome of a baculovirus pathogenic for Lymantria dispar.

The genome of the Lymantria dispar multinucleocapsid nucleopolyhedrovirus (LdMNPV) was sequenced and analyzed. It is composed of 161,046 bases with a G + C content of 57.5% and contains 163 putative open reading frames (ORFs) of >/=150 nucleotides.

Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignment.

Expressed sequence tag information was used to clone the full-length sequence for a new human lipoxygenase from the B cell line CCL-156. A related mouse sequence with 83% nucleotide identity to the human sequence was also cloned. The human lipoxygenase, when expressed via the baculovirus/insect cell system produced an approximately 80-kDa protein capable of metabolizing arachidonic acid to a product identified as 12-hydroxyeicosatetraenoic acid by mass spectrometry.

Determinants of 5-lipoxygenase nuclear localization using green fluorescent protein/5-lipoxygenase fusion proteins.

5-Lipoxygenase catalyzes the first two steps in the biosynthesis of leukotrienes, potent extracellular mediators of inflammation and allergic disorders. The unanticipated observation of 5-lipoxygenase in the nucleus of some cell types including bone marrow-derived mast cells (Chen, X. S.

Engineering of N-terminal threonines in the D1 protein impairs photosystem II energy transfer in Synechocystis 6803.

Mutants of the cyanobacterium Synechocystis sp. PCC 6803 with N-terminal changes in the photosystem (PSII) II D1 protein were analysed by flash-induced oxygen evolution, chlorophyll a fluorescence decay kinetics and 77 K fluorescence emission spectra. The data presented here show that mutations of the Thr-2, Thr-3 and Thr-4 in D1 do not influence the oxygen evolution.

[Functional MRT of the LS in an open magnet system--the initial results].

Purpose: Description of the procedure and first results with functional MRI of the lumbar spine for the investigation of discoligamentous instability.

Material And Method: 21 patients--11 female and 10 male--were studied with rapid True-FISP- and FLASH sequences. With the intention to document movements in maximal ante- and retroflexion a special kidney belt was used containing an inserted multi-purpose flexible coil.

Cloning of a human "epidermal-type" 12-lipoxygenase-related gene and chromosomal localization to 17p13.

A human "epidermal-type" 12-lipoxygenase (e-12LO) pseudogene was cloned using a murine e-12LO cDNA probe. Similar to other lipoxygenase genes, the genomic sequence revealed 14 exons and 13 introns covering 6.7 kb of DNA.

Evolving roles of life and health sciences librarians for the twenty-first century.

The twenty-first century will provide exciting challenges for life and health sciences librarians that will force us to redefine our position in the world of information. This rapidly changing environment influences the profession in a variety of ways including whom we serve and through what service, how and where we practice librarianship, and even the very composition of the profession itself. We must look at the changes in society and make the appropriate reciprocal changes in how we educate future librarians, how we market the profession, and how we develop the profession as a whole.

Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase.

Arachidonic acid metabolism is one of several mechanisms culminating in the production of an agonist for platelet activation and recruitment. Although the proaggregatory role of thromboxane A2, a product of the aspirin-inhibitable cyclooxygenase, is well established, relatively little is known regarding the biological importance of arachidonic acid metabolism via the 12-lipoxygenase (P-12LO) pathway to 12-hydro(pero)xyeicosatetraenoic acid. We observed that platelets obtained from mice in which the P-12LO gene has been disrupted by gene targeting (P-12LO-/-) exhibit a selective hypersensitivity to ADP, manifested as a marked increase in slope and percent aggregation in ex vivo assays and increased mortality in an ADP-induced mouse model of thromboembolism.

Differential stability of baculovirus late transcription complexes during initiation and elongation.

An in vitro system for baculovirus late transcription was developed that allows comparison of conditions that affect transcription initiation and elongation. A series of synthetic promoters was constructed based on the baculovirus late p6.9 promoter.

Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia.

Glutathione peroxidase, a selenium-containing enzyme, is believed to protect cells from the toxicity of hydroperoxides. The physiological role of this enzyme has previously been implicated mainly using animals fed with a selenium-deficient diet. Although selenium deficiency also affects the activity of several other cellular selenium-containing enzymes, a dramatic decrease of glutathione peroxidase activity has been postulated to play a role in the pathogenesis of a number of diseases, particularly those whose progression is associated with an overproduction of reactive oxygen species, found in selenium-deficient animals.

5-Lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice.

To determine the role of 5-lipoxygenase products in the development of airway reactivity that follows antigen exposure, we sensitized mice by intraperitoneal injection of ovalbumin and aluminum hydroxide and serial exposure to aerosols of ovalbumin. Mice lacking a functioning 5-lipoxygenase enzyme were produced by targeted gene disruption. They and their wild-type controls had measurements of lung resistance (RL) made in response to intravenous methacholine; bronchoalveolar lavage fluid cell counts and serum immunoglobulin concentrations were also measured.

Interleukin-4 modulates cholinergic neural control of mouse small intestinal longitudinal muscle.

Interleukin-4 contributes to expulsion of certain gastrointestinal parasites and causes intestinal mucosal mastocytosis. Because mast cell-derived mediators are spasmogenic, potentially causing parasitic expulsion, we investigated the effect of interleukin-4 on smooth muscle and the mast cell and mediator dependency of this effect. BALB/c, mast cell-deficient W/Wv mice, 5-lipoxygenase-efficient mice, and their littermate controls were injected with interleukin-4-anti-interleukin-4 antibody complexes that chronically increase serum interleukin-4 levels.

The sequence of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus genome.

The nucleotide sequence of the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV) genome was completed and analyzed. It is composed of 131,990 bases with a G + C content of 55% and contains 152 putative genes of 150 nucleotides or greater. Major differences in gene content and arrangement between OpMNPV and the Autographa californica MNPV were found.

Association of a baculovirus-encoded protein with the capsid basal region.

An open reading frame homologous to AcMNPV ORF9 (ORF1629) was characterized in the Orgyia pseudotsugata multinucleocapsid nuclear polyhedrosis virus (OpMNPV). Sequence analysis indicated that the OpMNPV homolog (called ORF2) encoded a protein predicted to contain 545 amino acids with a molecular weight of 61 kDa. The first 80 amino acids did not have a counterpart in the AcMNPV homolog.

Human tumor models in the severe combined immune deficient (scid) mouse.

Purpose: To test a number of established human tumor cell lines and early passage breast cancer (UACC2150) and melanoma cells (UACC1273) for growth in the scid mouse and the tumors' response to conventional chemotherapeutic drugs.

Methods: Established melanoma (A375, C81-61), colon (SW480), lung (A549), lymphomoblastoid leukemia (LCL-B), promyelocytic leukemia (HL60), prostate (PC-3, DU145), and breast (MCF7) cell lines were injected at subcutaneous (s.c.

Prednisone increases PGH-synthase 2 in atopic humans in vivo.

We compared the expression of prostaglandin H synthase-2 (PGHS-2, cyclooxygenase) message and protein in alveolar macrophages (AM) and blood monocytes (BM) from 20 atopic subjects (AS) and nine control subjects (CS) at baseline and after 1 to 14 d of oral administration of therapeutic doses of prednisone. At baseline, the amounts of PGHS-2 mRNA in AM and BM varied within a similar range among subjects from each group. PGHS-2 protein was present in AM and BM from most AS, but it was also present in CS.

Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers.

To determine the metabolic profile of minimally absorbed orlistat in obese/overweight patients, an open-label, single-dose study was performed in eight obese/overweight volunteers between 23 and 68 years of age. Each subject received a single oral dose of 360 mg orlistat containing approximately 400 muCi of 14C-labeled orlistat. Serial blood samples were collected at specified times over 10 hours after administration of orlistat for determination of total radioactivity, unchanged orlistat, and major metabolites in the plasma.

Collaboration in a continuum of learning: developing the next generation of leadership.

A project to create a lifelong learning community among health sciences library and information professionals by demonstrating the potential for using complementary technologies to provide access to a full range of educational experiences as recommended in Platform for Change, the Medical Library Association's educational policy statement, is described. The cooperative project brings together the rich continuing education tradition of the Medical Library Association, the experience of the University of South Carolina in distance education, and the Library and Information Science Distance Education Consortium to create a virtual campus through which health sciences library professionals may engage in lifelong learning.

Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoprotein.

Previously, we isolated the murine "leukocyte-type" 12-lipoxygenase (L-12LO) cDNA from RNA of peritoneal-elicited cells that consisted predominantly of leukocytes (Chen, X.-S., Kurre, U.

Functional expression and cellular localization of a mouse epidermal lipoxygenase.

Three distinct murine lipoxygenase genes have been functionally characterized: 5-lipoxygenase (Chen, X.-S., Naumann, T.