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Biomedical subjects

M Rowe

Publications and source records attributed to M Rowe.

At least 19 recordsLinked to original sources
PubMed2006

A genomic view of the sea urchin nervous system.

The sequencing of the Strongylocentrotus purpuratus genome provides a unique opportunity to investigate the function and evolution of neural genes. The neurobiology of sea urchins is of particular interest because they have a close phylogenetic relationship with chordates, yet a distinctive pentaradiate body plan and unusual neural organization. Orthologues of transcription factors that regulate neurogenesis in other animals have been identified and several are expressed in neurogenic domains before gastrulation indicating that they may operate near the top of a conserved neural gene regulatory network. A family of genes encoding voltage-gated ion channels is present but, surprisingly, genes encoding gap junction proteins (connexins and pannexins) appear to be absent. Genes required for synapse formation and function have been identified and genes for synthesis and transport of neurotransmitters are present. There is a large family of G-protein-coupled receptors, including 874 rhodopsin-type receptors, 28 metabotropic glutamate-like receptors and a remarkably expanded group of 161 secretin receptor-like proteins. Absence of cannabinoid, lysophospholipid and melanocortin receptors indicates that this group may be unique to chordates. There are at least 37 putative G-protein-coupled peptide receptors and precursors for several neuropeptides and peptide hormones have been identified, including SALMFamides, NGFFFamide, a vasotocin-like peptide, glycoprotein hormones and insulin/insulin-like growth factors. Identification of a neurotrophin-like gene and Trk receptor in sea urchin indicates that this neural signaling system is not unique to chordates. Several hundred chemoreceptor genes have been predicted using several approaches, a number similar to that for other animals. Intriguingly, genes encoding homologues of rhodopsin, Pax6 and several other key mammalian retinal transcription factors are expressed in tube feet, suggesting tube feet function as photosensory organs. Analysis of the sea urchin genome presents a unique perspective on the evolutionary history of deuterostome nervous systems and reveals new approaches to investigate the development and neurobiology of sea urchins.

Animals↗
PubMed2003

Cyclic fed-batch culture for production of human serum albumin in Pichia pastoris.

Simple cyclic fed-batch culture (cfbc), consisting of a constant medium feed with periodic withdrawals of culture, resulted in a product yield (13.4 mg protein per gram biomass) similar to that obtained using the complex multiphase industrial production strategy (13.7 mg protein per gram biomass). In cfbc, productivity was ultimately limited by the rate at which the cells could assimilate methanol. Glycerol was inhibitory to growth at high concentrations. However, product yield continued to increase as the glycerol concentration was increased. In chemostat culture, dissolved oxygen concentration influenced product yield independently of any detectable influence on cell growth.

Bioreactors↗
PubMed2003

Experimental demonstration of a technique to generate arbitrary quantum superposition states of a harmonically bound spin-1/2 particle.

Using a single, harmonically trapped 9Be(+) ion, we experimentally demonstrate a technique for generation of arbitrary states of a two-level particle confined by a harmonic potential. Rather than engineering a single Hamiltonian that evolves the system to a desired final state, we implement a technique that applies a sequence of simple operations to synthesize the state.

Journal Article↗
PubMed2002

Experimental demonstration of a controlled-NOT wave-packet gate.

We report the experimental demonstration of a controlled-NOT (CNOT) quantum logic gate between motional and internal-state qubits of a single ion where, as opposed to previously demonstrated gates, the conditional dynamics depends on the extent of the ion's wave packet. Advantages of this CNOT gate over one demonstrated previously are its immunity from Stark shifts due to off-resonant couplings and the fact that an auxiliary internal level is not required. We characterize the gate logic through measurements of the postgate ion state populations for both logic basis and superposition input states, and we demonstrate the gate coherence via an interferometric measurement.

Journal Article↗
PubMed2002

Trapped-ion quantum simulator: experimental application to nonlinear interferometers.

We show how an experimentally realized set of operations on a single trapped ion is sufficient to simulate a wide class of Hamiltonians of a spin-1/2 particle in an external potential. This system is also able to simulate other physical dynamics. As a demonstration, we simulate the action of two nth order nonlinear optical beam splitters comprising an interferometer sensitive to phase shift in one of the interferometer beam paths. The sensitivity in determining these phase shifts increases linearly with n, and the simulation demonstrates that the use of nonlinear beam splitters (n=2,3) enhances this sensitivity compared to the standard quantum limit imposed by a linear beam splitter (n=1).

Journal Article↗
PubMed2002

"Medical bookmarks--a virtual medical library".

How does one go about finding specific medical information on the internet? Medical Bookmarks is the name of an easily remembered website (http://www.medical-bookmarks.org.uk) set up as a virtual library by the librarian at the Royal Hospital Haslar. It is specifically designed to give easy access to all the important medical sites on the internet, doing away with the need to remember the exact addresses of other websites, and as such it is relevant to civilian and military doctors in both industrialised and developing nations. It also interlinks sites of particular relevance to military doctors, including military medical sites and a NATO Defence Medical Services site.

Information Services↗
PubMed2001

Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.

CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL. INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups. CONCLUSION: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.

Adolescent↗
PubMed2001

Characterization of a CD40-dominant inhibitory receptor mutant.

CD40 is an important mediator of immune and inflammatory responses. It is a costimulatory molecule for B cell proliferation and survival. Blockade of CD40 has been shown to induce tolerance and its role in other pathogenic conditions has led to the proposal that CD40 inhibition could be valuable therapeutically. As a first step to this end, we have characterized a CD40-dominant negative receptor. This inhibitory mutant lacks the identified CD40 signaling domains. It inhibits both cotransfected and endogenous CD40 activation of NF-kappaB. This mutant is specific, as it does not affect TNF or latent membrane protein 1 signaling. Its potential usefulness is illustrated by its ability to inhibit the CD40 ligand-stimulated increases of HLA and CD54 expression, molecules involved in Ag recognition and lymphocyte recruitment leading to organ rejection. The inhibitory mutant has no TNFR-associated factor 2-binding capabilities and inhibits the recruitment of TNFR-associated factor 2 to the CD40 signaling complex after stimulation. These studies show that the CD40 inhibitory receptor molecule is effective, specific, and useful both for research and potentially as a clinical tool. And furthermore, it is likely that similar dominant inhibitory receptors can be generated for all of the members of the TNFR superfamily.

Binding Sites↗
PubMed2001

Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6.

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with the development of cervical cancer. The E6 and E7 proteins of HPV are constitutively expressed in cervical carcinoma cells making them attractive targets for CTL-based immunotherapy. However, few studies have addressed whether cervical carcinomas can process and present HPV E6/E7-derived Ags for recognition by CTL. We generated HLA-A*0201-restricted CTL clones against HPV16 E6(29-38) that recognized HPV16 E6 Ags transfected into B lymphoblastoid cells. These CTL were unable to recognize HLA-A*0201(+) HPV16 E6(+) cervical carcinoma cell lines even when the level of endogenous HPV16 E6 in these cells was increased by transfection. This defect in presentation of HPV16 E6(29-38) correlated with low level expression of HLA class I, proteasome subunits low molecular mass protein 2 and 7, and the transporter proteins TAP1 and TAP2 in the cervical carcinoma cell lines. The expression of all of these proteins could be up-regulated by IFN-gamma, but this was insufficient for CTL recognition unless the level of HPV16 E6 Ag was also increased by transfection. CTL recognition of the HPV16 E6(29-38) epitope in 721.174 B cells was dependent on TAP expression but independent of immunoproteasome expression. Collectively, these findings suggest that presentation of the HPV16 E6(29-38) epitope in cervical carcinoma cell lines is limited both by the level of TAP expression and by the low level or availability of the source HPV E6 oncoprotein. These observations place constraints on the use of this, and potentially other, HPV-derived CTL epitopes for the immunotherapy of cervical cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

CD99 expression is positively regulated by Sp1 and is negatively regulated by Epstein-Barr virus latent membrane protein 1 through nuclear factor-kappaB.

Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) is highly expressed in Hodgkin and Reed-Sternberg (H-RS) cells from patients with EBV-associated Hodgkin disease. It was previously demonstrated that CD99 can be negatively regulated by LMP1 at the transcriptional level, and the decreased expression of CD99 in a B lymphocyte cell line generates H-RS-like cells. In this study, detailed dissection of the CD99 promoter region was performed to search regulatory factor(s) involved in the expression of the gene. Using various mutant constructs containing deletions in the promoter region, it was revealed that the maximal promoter activity was retained on 5'-deletion to the position -137 from the transcriptional initiation site. Despite the presence of multiple putative Sp1-binding sites in the promoter region, the site located at -95 contributes heavily as a positive cis-acting element to its basal promoter activity. However, on examination of the involvement of the positive-acting Sp1-binding site of the promoter for the repressive activity of LMP1, it appeared to be dispensable. Instead, the repressive effect was mapped to the nuclear factor (NF)-kappaB activation domains in the cytoplasmic carboxyl terminus of LMP1 despite the absence of the NF-kappaB consensus sequences in the CD99 promoter region. Furthermore, the decreased CD99 promoter activity by LMP1 was markedly restored when NF-kappaB activity was inhibited. Taken together, these data suggest that Sp1 activates, whereas LMP1 represses, transcription from the CD99 promoter through the NF-kappaB signaling pathway, and they might aid in the understanding of the molecular mechanisms of viral pathogenesis in EBV-positive Hodgkin disease. (Blood. 2001;97:3596-3604)

12E7 Antigen↗
PubMed2001

Impact of early percutaneous coronary intervention on short- and long-term outcomes in patients with cardiogenic shock after acute myocardial infarction.

This study assesses the impact of early percutaneous coronary intervention in patients presenting with cardiogenic shock after acute myocardial infarction. Predictors of in-hospital death include the need for intubation, cardiopulmonary resuscitation, and angiographic failure; long-term outcomes at 2 years in hospital survivors are favorable.

Aged↗
PubMed2001

Characterization of intercellular adhesion molecule-1 regulation by Epstein-Barr virus-encoded latent membrane protein-1 identifies pathways that cooperate with nuclear factor kappa B to activate transcription.

The latent membrane protein-1 (LMP1) of Epstein-Barr virus induces gene transcription, phenotypic changes, and oncogenic transformation. One cellular gene induced by LMP1 is that for intercellular adhesion molecule-1 (ICAM-1), which participates in a wide range of inflammatory and immune responses. ICAM-1 may enhance the immune recognition of cells transformed by Epstein-Barr virus, and thus combat development of malignancy. Despite growing understanding of the various signaling functions of LMP1, the molecular mechanisms by which LMP1 induces ICAM-1 are not understood. Here, we demonstrate that transcriptional activation by LMP1 is absolutely dependent upon a variant NF-kappaB motif within the tumor necrosis factor alpha (TNFalpha) response element of the ICAM-1 promoter. Although the TNFalpha response element is sufficient for TNFalpha induction of the ICAM-1 promoter, LMP1 also required the cooperation of additional upstream sequences for optimal induction. Inhibitor studies of known LMP1-induced signaling pathways ruled out the involvement of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and the Janus-activating tyrosine kinase 3 (JAK3), and confirmed NF-kappaB as a critical factor for induction of ICAM-1. However, although constitutive activation of NF-kappaB efficiently induced promoter activity, it was not sufficient to induce either ICAM-1 mRNA or ICAM-1 protein. Using signaling defective LMP1 mutants and deacetylation inhibitors, we showed that the C-terminal activator region 1 of LMP1 delivers a new cooperating signal to induce ICAM-1 mRNA.

B-Lymphocytes↗
PubMed2001

Mechanism of action of a novel latent membrane protein-1 dominant negative.

Latent membrane protein-1 (LMP1) is a signaling molecule expressed by Epstein-Barr virus during latency. LMP1 is essential for B-cell immortalization by Epstein-Barr virus and transforms rodent fibroblasts. It activates many distinct signaling pathways including the transcription factors NFkappaB and AP1. We have generated a mutant of LMP1 with four point mutations; amino acids 204, 206, and 208 were mutated to alanine, and amino acid 384 was mutated to glycine. This mutant, termed LMP1(AAAG), is not only unable to activate nuclear signaling pathways, but also inhibits signaling from wild type LMP1. We have demonstrated the effectiveness, selectivity, and mechanism of this inhibitory molecule. It inhibits LMP1-stimulated NFkappaB, STAT, and Jun transcriptional activity. It is selective, as it does not inhibit TNF or interleukin-2 signaling. We have demonstrated that it does not sequester the downstream signaling molecule, TRAF2, but instead binds LMP1 and interferes with its ability to bind TRAF2. This demonstrates the importance of the interplay between the signaling domains of LMP1 and the oligomeric structure of LMP1 for effective signaling. It identifies a tool that will be useful to probe LMP1 function in disease.

Alanine↗
PubMed2001

Composition and chirality of amino acids in aerosol/dust from laboratory and residential enclosures.

Initial results from the analyses of geological and anthropological samples for amino acids were difficult to accept because of the high enantiomeric purities of the analytes (i.e., predominantly L-amino acids). Consequently, sources of contamination had to be considered. All sources were eliminated except for direct atmospheric contamination. Essentially invisible, microscopic, aerosol/dust was found to rapidly contaminate the surface of samples and sample containers even after brief exposure times in clean laboratories. Contamination increased with exposure time. The aerosol/dust amino acids were contained predominantly in a proteinaceous material. Aerosol/dust from different locations can contain different percentages of proteinoid/amino acid material. However, the relative concentrations of the amino acids were similar for both laboratory and residential samples. The enantiomeric purity of the L-amino acids studied in aerosol/dust appears to be 99% or greater for the samples examined. Thus, even slight contamination of any sample with microscopic dust or aerosol particles can skew the results of trace amino acid analyses and amino acid e.e. determinations.

Aerosols↗
PubMed2001

Mental health training in emergency homeless shelters.

The prevalence of mental illness among homeless persons points to the importance of providing mental health training to emergency shelter staff. The authors report on their own work and argue that such training offers the potential to significantly improve shelter staffs ability to respond to the needs of shelter residents with mental illness, and to the behavioral problems some of these individuals may pose for shelter operation. Mental health care providers should take into consideration organizational dynamics when planning and implementing such training.

Case Management↗
PubMed2001

Clinical responsibility and client autonomy: dilemmas in mental health work at the margins.

Mental health outreach to homeless persons requires practice standards for cases in which clinical assessment and client autonomy conflict. After reviewing the principles of mental health outreach and presenting case examples, conditions and boundaries within which outreach workers negotiate the clinical responsibility/client autonomy dilemma are discussed. Guidelines to support sound clinical practice while respecting client autonomy are also discussed.

Community-Institutional Relations↗
PubMed2001

"Simply to be let in": inclusion as a basis for recovery.

This article takes its inspiration from a poem by Borges, in which the author makes a plea to simply be "let in" without being wondered at or required to succeed. Based on the view that these issues have applied historically to people with mental illnesses--first during the period of the asylum, and now more recently as a result of deinstitutionalization--this article argues for the adoption of a broad conceptual framework of inclusion that, based on a disability paradigm, neither alienates or requires people to succeed. First, the ways in which such a framework augments existing approaches to treatment, rehabilitation, and recovery are outlined. Next, the authors describe the three elements of friendship, reciprocity, and hopefulness as aspects of inclusion that may provide a foundation for efforts toward recovery, and illustrate each of these elements through the stories of participants in a supported socialization program. Implications for future research and policy are suggested based on these data.

Convalescence↗