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Biomedical subjects

J E Murphy

Publications and source records attributed to J E Murphy.

At least 19 recordsLinked to original sources
PubMed2001

Perceived value and outcomes of residency projects.

Residency program directors' attitudes toward residency projects were studied. A questionnaire about the residency project experience was mailed in January 2000 to 446 pharmacy practice residency program and specialty residency program directors in the program database of the American Society of Health-System Pharmacists. Recipients responded to opinion statements on a 5-point scale. Responses to the opinion statements were separated into seven categories for analysis. A total of 278 usable questionnaires were returned, for a raw response rate of 63.6%. During the preceding three years, residency directors had served as primary advisors on 917 projects; 171 had served as advisor on at least one of every type of project allowed in the accreditation standards. Of the 917 projects, 364 were presented at national professional meetings, 124 were published, and 484 were believed to have resulted in a positive change in pharmacy services. There were no significant differences in total response scores among any of the subgroups analyzed. There was strong agreement that residency projects were valuable and should continue to be part of the residency program experience. The directors' views of the importance of original research as a project option were more neutral. Overall residency program directors had positive perceptions of the value of residency projects to both residents and institutions and believed that they should continue to be a requirement of residency programs.

Administrative Personnel↗
PubMed2001

Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin.

Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.

Adult↗
PubMed2000

Characterization of heterodimeric alkaline phosphatases from Escherichia coli: an investigation of intragenic complementation.

Escherichia coli alkaline phosphatase (EC 3.1.3.1) belongs to a rare group of enzymes that exhibit intragenic complementation. When certain mutant versions of alkaline phosphatase are combined, the resulting heterodimeric enzymes exhibit a higher level of activity than would be expected based upon the relative activities of the parental enzymes. Nine previously identified alkaline phosphatase complementation mutants were re-examined in this work in order to determine a molecular explanation of intragenic complementation in this experimental system. The locations of these mutations were determined by DNA sequence analysis after PCR amplification of the phosphatase-negative phoA gene. Most of the mutations involved ligands to metal-binding sites. Each of the mutant enzymes was re-created by site-specific mutagenesis, expressed, purified, and kinetically characterized. To investigate cooperativity between the two subunits, we analyzed heterodimeric forms of some of the site-specific mutant enzymes. To enable the isolation of the heterodimeric alkaline phosphatase in pure form, the overall charge of one subunit was altered by replacing the C-terminal Lys residue with three Asp residues. This modification had no effect on the kinetic properties of the enzyme. Heterodimeric alkaline phosphatases were created using two methods: (1) in vitro formation by dissociation at acid pH followed by reassociation at slightly alkaline pH conditions in the presence of zinc and magnesium ions; and (2) in vivo expression from a plasmid carrying two different phoA genes. Increases in k(cat), as well as a large reduction in the p-nitrophenyl phosphate K(m) were observed for certain combinations of mutant enzymes. These results suggest that the structural assembly of E. coli alkaline phosphatase into the dimer induces cooperative interactions between the monomers necessary for the formation of the functional form of the holoenzyme.

Alkaline Phosphatase↗
PubMed2000

Using benchmarking data to evaluate and support pharmacy programs in health systems.

The use of benchmarking data to evaluate and support pharmacy programs in health systems is discussed. Benchmarking is a method of comparing the outcomes of health care products, services, and practices at an institution against those of competitors in order to learn what might be improved. Benchmarking programs can provide valuable feedback about both positive and negative outcomes. However, it is imperative to avoid inappropriate comparisons and inappropriate assessments. Ideal services for benchmarking are those that have a good likelihood of improving patient care and other outcomes. Successful benchmarking requires sound and thorough data, which is why as many health systems as possible should participate in a benchmarking program. The National Committee for Quality Assurance has formulated guidelines that should enable health systems to develop an information framework that will improve their ability to collect and use data for benchmarking. Standardization in collecting and submitting information is important because it enables institutions to share data easily. Benchmarking can help health-system pharmacists understand the value and outcomes of efforts by their colleagues at other institutions. In addition, benchmarking can help convince health-system administrators of the value of pharmaceutical services in terms of patient care and the bottom line. Benchmarking provides a means of evaluating and supporting the development of pharmacy programs that improve care and save money.

Benchmarking↗
PubMed2000

Overexpression of Bcl-2 protects from ultraviolet B-induced apoptosis but promotes hair follicle regression and chemotherapy-induced alopecia.

Hair follicle (HF) growth and regression is an exquisitely regulated process of cell proliferation followed by massive cell death and is accompanied by cyclical expression of the apoptosis regulatory gene pair, Bcl-2 and Bax. To further investigate the role of Bcl-2 expression in the control of hair growth and keratinocyte apoptosis, we have used transgenic mice that overexpress human Bcl-2 in basal epidermis and in the outer root sheath under the control of the human keratin-14 promoter (K14/Bcl-2). When irradiated with ultraviolet B (UVB) light, K14/Bcl-2 mice developed about 5-10-fold fewer sunburn cells (ie, apoptotic keratinocytes) in the basal layer of the epidermis, compared to wild-type mice, whereas cultures of primary keratinocytes from transgenic mice were completely resistant to UVB-induced histone formation, at doses that readily induced histone release from wild-type cells. K14/Bcl-2 mice show no alteration of neonatal hair follicle morphogenesis or of the onset of the first wave of HF regression (catagen). However, compared to wild-type controls, K14/Bcl-2 mice subsequently displayed a significant acceleration of spontaneous catagen progression. During chemotherapy-induced alopecia, follicular dystrophy was promoted in K14/Bcl-2 mice. Thus, although K14-driven overexpression of Bcl-2 protected murine epidermal keratinocytes from UVB-induced apoptosis, it surprisingly promoted catagen- and chemotherapy-associated keratinocyte apoptosis.

Alopecia↗
PubMed2000

Profiling of genes which are differentially expressed in mouse liver in response to adenoviral vectors and delivered genes.

The effects of transgene delivery by adenoviral vectors were studied by probing a 588 gene, mouse cDNA array with mRNA derived from infected liver. The liver tissues were obtained from naive mice and mice infected with replication-deficient adenovirus, adenovirus expressing transforming growth factor beta1 (TGFbeta1), and adenovirus expressing connective tissue growth factor (CTGF). Expression of 98 genes was detected in the array analysis. The increased expression of the transcripts for Stat1, gamma interferon-induced monokine (MIG) and interferon regulatory factor 1 (IRF1) clearly demonstrated the immune response induced by infection with a first generation, replication-incompetent adenovirus. In vivo expression of TGFbeta1 led to a down-regulation of genes involved in the immune response. The increased expression of u-PAR1, laminin receptor and BMP-1 confirms the importance of CTGF and TGFbeta1 in angiogenesis, and tissue repair. Expression of the serine protease inhibitors, Spi 2.4 and Spi 2, is also increased in response to AdTGFbeta1 and AdCTGF.

Adenoviridae↗
PubMed2000

Interleukin-1 and cutaneous inflammation: a crucial link between innate and acquired immunity.

As our primary interface with the environment, the skin is constantly subjected to injury and invasion by pathogens. The fundamental force driving the evolution of the immune system has been the need to protect the host against overwhelming infection. The ability of T and B cells to recombine antigen receptor genes during development provides an efficient, flexible, and powerful immune system with nearly unlimited specificity for antigen. The capacity to expand subsets of antigen-specific lymphocytes that become activated by environmental antigens (memory response) is termed "acquired" immunity. Immunologic memory, although a fundamental aspect of mammalian biology, is a relatively recent evolutionary event that permits organisms to live for years to decades. "Innate" immunity, mediated by genes that remain in germ line conformation and encode for proteins that recognize conserved structural patterns on microorganisms, is a much more ancient system of host defense. Defensins and other antimicrobial peptides, complement and opsonins, and endocytic receptors are all considered components of the innate immune system. None of these, however, are signal-transducing receptors. Most recently, a large family of cell surface receptors that mediate signaling through the NF-kappaB transcription factor has been identified. This family of proteins shares striking homology with plant and Drosophila genes that mediate innate immunity. In mammals, this family includes the type I interleukin-1 receptor, the interleukin-18 receptor, and a growing family of Toll-like receptors, two of which were recently identified as signal-transducing receptors for bacterial endotoxin. In this review, we discuss how interleukin-1 links the innate and acquired immune systems to provide synergistic host defense activities in skin.

Antibody Formation↗
PubMed1999

A call to arms.

Explore the source record for details and available documents.

Pharmacists↗
PubMed1999

Research experiences and research-related coursework in the education of doctors of pharmacy.

A study assessed coursework and experiential activities of students to determine the role of research in Doctor of Pharmacy education. Questionnaires were sent to all 78 (at that time) colleges and schools of pharmacy in the United States. Responses were received from 60 (76.9%), of which 57 were used, representing 139 Pharm.D. program types (entry-level, post-B.S., track-in, nontraditional). Most programs required coursework in research methodology, statistics, and drug information and literature evaluation, with research methodology required least. Although 41.0% of programs provided students the opportunity to conduct research as an elective, only 12.9% required an extensive project with data collection, analysis, and write-up. Another 6.5% required a project proposal only. Most colleges of pharmacy now offer the Pharm.D. degree, and the role of the pharmacist has also changed. Pharmacists must be able to disseminate evidence-based knowledge about drug products and drug therapy and use scientific knowledge and scholarly principles to solve problems.

Curriculum↗
PubMed1998

Evaluation of gentamicin pharmacokinetics and dosing protocols in 195 neonates.

Gentamicin pharmacokinetics and dosing protocols in neonates were studied. Demographic and pharmacokinetic data on 202 neonates treated with gentamicin at a 500-bed medical center were collected over a three-year period. Administered doses, gentamicin concentration measurements, and recorded times were used to calculate each patient's clearance, volume of distribution, elimination rate constant, and half-life. The performance of 15 dosing protocols, including 6 previously published ones and 9 developed on the basis of the study, was evaluated using the pharmacokinetic data. Of the 202 patients, 195 were included in the analysis. The mean +/- S.D. clearance, volume of distribution, elimination rate constant, and half-life were 0.047 +/- 0.015 L/hr/kg, 0.45 +/- 0.11 L/kg, 0.107 +/- 0.032 L/hr, and 7.19 +/- 2.64 hours, respectively. Weight, urine output, gestational age, and postconceptional age (PCA) had the highest correlation with the pharmacokinetic values. Blood urea nitrogen concentration (BUN) and Apgar score were poor predictors of the pharmacokinetic values. There were no significant differences among patient subsets based on race and BUN, but subset analysis based on PCA did indicate significant differences. In simulations, the protocols based on the study patients tended to perform better than the literature protocols, with all but three achieving therapeutic goals in 75% or more of the neonates. Of the published protocols, Murphy and Carter's produced the greatest percentage of neonates with peaks from 5 to 10 mg/L and troughs of <2 mg/L. The devised protocols tended to perform poorly in producing troughs between 1 and 2 mg/L, yet performed comparatively well in providing therapeutic peaks from 5 to 10 mg/L.

Body Weight↗
PubMed1998

A combinatorial approach to the discovery of efficient cationic peptoid reagents for gene delivery.

A family of N-substituted glycine oligomers (peptoids) of defined length and sequence are shown to condense plasmid DNA into small particles, protect it from nuclease degradation, and efficiently mediate the transfection of several cell lines. The oligomers were discovered by screening a combinatorial library of cationic peptoids that varied in length, density of charge, side-chain shape, and hydrophobicity. Transfection activity and peptoid-DNA complex formation are shown to be highly dependent on the peptoid structure. The most active peptoid is a 36-mer that contains 12 cationic aminoethyl side chains. This molecule can be synthesized efficiently from readily available building blocks. The peptoid condenses plasmid DNA into uniform particles 50-100 nm in diameter and mediates the transfection of a number of cell lines with efficiencies greater than or comparable to DMRIE-C, Lipofectin, and Lipofectamine. Unlike many cationic lipids, peptoids are capable of working in the presence of serum.

3T3 Cells↗
PubMed1998

Use of a recombinant murine cytomegalovirus expressing vesicular stomatitis virus G protein to pseudotype retroviral vectors.

A new method of producing vesicular stomatitis virus (VSV) G protein pseudotyped retroviral vectors is described. In this method, stocks of VSV-G pseudotyped vector were reproducibly obtained by infecting an env-, human, retroviral vector producer cell line with a recombinant murine cytomegalovirus (CMV) which expresses VSV-G protein. The recombinant murine CMV, RMCMVG, expressed VSV-G protein under transcriptional control of the human CMV immediate-early promoter. RMCMVG, like murine CMV, can infect human cells, but the infection is limited to the expression of the viral immediate-early genes; no productive replication of murine CMV occurs. Recombinant murine CMV vector infection of non-permissive cells may be useful in situations where high levels of gene expression are desired without concomitant viral vector replication.

3T3 Cells↗
PubMed1998

Lipitoids--novel cationic lipids for cellular delivery of plasmid DNA in vitro.

BACKGROUND: Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro. RESULTS: Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA into 100 nm spherical particles and protected the DNA and DNase digestion. A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency. CONCLUSIONS: Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potential for applications in vivo.

3T3 Cells↗