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Biomedical subjects

B Gibbs

Publications and source records attributed to B Gibbs.

17 recordsLinked to original sources
PubMed2002

Development of a laser safety hazard evaluation procedure for the research university setting.

Laser safety often receives less attention and fewer resources than other institutional safety and health program elements. This diminished support occurs despite the fact that the potential for laser-related occupational injuries is much greater than the potential for injury from radioactive materials used in biomedical research. Therefore, a small emphasis on laser safety can potentially produce a much greater return on investment than more conventional health physics programs. Developing and implementing a formal laser hazard evaluation procedure provides all efficient mechanism for identifying potential laser safety hazards and offers a great professional development opportunity in this important area of health physics expertise. This paper outlines a process for developing such a university laser hazard evaluation program.

Forms and Records Control↗
PubMed2001

Reducing risk.

Explore the source record for details and available documents.

Guidelines as Topic↗
PubMed2000

Nerve growth factor-beta induces mast-cell marker expression during in vitro culture of human umbilical cord blood cells.

Nerve growth factor-beta (NGF) is known as a growth factor for human basophils and murine mast cells and has recently been shown to also up-regulate mast cell characteristics in human leukaemic mast cells. We have examined here the effect of NGF on the differentiation of normal human mast cells from cord blood progenitors during culture with stem cell factor (SCF), NGF alone or in combination, or fibroblast supernatants. All these supplements induced mast cell immunoreactivity against tryptase, c-Kit and FcepsilonRIalpha, but none of the cells reacted against the basophil specific antibody 2D7 before or during culture. Intracellular tryptase activity increased as well, with maximal levels on combined culture with SCF and NGF. On reverse transcription-polymerase chain reaction (RT-PCR), cells lacked tryptase and chymase and expressed low levels of FcepsilonRI and c-Kit mRNA prior to culture, with marked up-regulation of FcepsilonRI and c-Kit, and with de novo expression of mast-cell specific alpha- and beta-tryptase by week 3, and of chymase by week 5. Only the TrkA and not the p75 NGF receptor was detected at m-RNA and protein level, and only the TrkA NGF receptor was up-regulated during NGF-driven culture. These findings show therefore that, like SCF, NGF is another growth factor that can induce and regulate human mast-cell development and differentiation.

Biomarkers↗
PubMed1999

Human mast cells produce and differentially express both soluble and membrane-bound stem cell factor.

Stem cell factor (SCF), characterized as mast cell growth factor, is known to be produced by fibroblasts, keratinocytes and endothelial cells. Two different splice variants encode for either a soluble (SCF-1) or a membrane-bound (SCF-2) form. In order to explore whether mast cells themselves can produce SCF, we examined cultured cord blood (CBMC) and peripheral-blood-derived mast cells (PBMC), mast/basophil cell lines (HMC-1 and KU-812), and skin mast cells for SCF expression. On immunocytochemistry, cytoplasmatic SCF-reactivity was observed in HMC-1 cells, with additional cell membrane staining in KU-812, skin and cultured mast cells. Low amounts of SCF could be detected by ELISA in lysates of isolated and unstimulated mast cells and in supernatants of skin cells stimulated with anti-IgE or Ca-ionophore A23187. SCF mRNA was detected in all cells, although marked quantitative differences were observed among the various cell types. SCF-2 mRNA expression was low in HMC-1 cells while it was marked in skin mast cells, KU-812 cells, CBMC and PBMC. A time-dependent, increasing induction of both SCF forms was seen in CBMC and PBMC during culture. After stimulation with A23187 and phorbol myristate acetate, an up-regulation of SCF mRNA was noted in HMC-1 and KU-812 cells, without changes in the relationship of the two splice variants. The differential expression of SCF-specific mRNA splice variants in immature and mature human mast cells and the secretion of this molecule by these cells may play a role in autocrine stimulation, maintenance of survival and the differentiation of tissue mast cells.

Cell Line↗
PubMed1997

Hepatitis C virus infection rate in volunteer blood donors from the Western Cape--comparison of screening tests and PCR.

INTRODUCTION: Hepatitis C virus (HCV) antibody seroprevalence studies overestimate the true infection rate. No data exist on the incidence of HCV or its clinical features in blood donors of sub-Saharan Africa. AIMS: To establish the true incidence of HCV infection in volunteer blood donors in the Western Cape, and compare risk factors and clinical and biochemical features of viraemic and non-viraemic subjects. METHODS: All donors attending the Western Province Blood Transfusion Service between December 1992 and August 1994 were screened prospectively for anti-HCV using the Abbott second-generation assay. Positive donors were evaluated clinically and biochemically. Their sera were examined for HCV-RNA by the polymerase chain reaction (PCR). RESULTS: Of 66314 donors screened, 275 (0.41%) were anti-HCV-positive. Of these 13.6% were PCR-positive (0.056% of all donors). PCR-positive patients had more risk factors for HCV acquisition (P < 0.01), symptoms of hepatitis (P = 0.02) and clinical signs of liver disease (P = 0.05) and higher alanine (P < 0.0001) and aspartate aminotransferase levels (P < 0.0001) than PCR-negative donors. However, clinical and biochemical features did not discriminate adequately between PCR-positive and negative donors. Liver biopsies performed in 9 of 13 PCR-positive cases showed mild inflammation, but no cirrhosis.

Blood Donors↗
PubMed1996

Candidate gene acting as a suppressor of the RH locus in most cases of Rh-deficiency.

The Rh antigen is a multi-subunit complex composed of Rh polypeptides and associated glycoproteins (Rh50, CD47, LW and glycophorin B); these interact in the red cell membrane and are lacking or severely reduced in Rhnull cells. As a result, individuals with Rhnull suffer chronic haemolytic anaemia known as the Rh-deficiency syndrome. Most frequently, Rhnull phenotypes are caused by homozygosity of an autosomal suppressor gene unlinked to the RH locus (Rhnull regulator or Rhmod types). We have analysed the genes and transcripts encoding Rh, CD47 and Rh50 proteins in five such unrelated Rhnull cases. In all patients, we identified alteration of Rh50--frameshift, nucleotide mutations, or failure of amplification--which correlated with Rhnull phenotype. We propose that mutant alleles of Rh50, which map to chromosome 6p11-21.1, are likely candidates for suppressors of the RH locus accounting for most cases of Rh-deficiency.

Amino Acid Sequence↗
PubMed1995

The role of the clinical nurse specialist and the nurse manager in case management.

Nursing case management was introduced into the acute care hospital as an approach to counteract the numerous changes occurring in the healthcare environment negatively affecting patient care. The authors address the development of case management at Bergan Mercy Medical Center, Omaha, Nebraska, and the integration of the nurse manager and clinical nurse specialist into this model.

Hospital Information Systems↗
PubMed1993

An improved FIA biosensor for the determination of aspartame in dietary food products.

A flow injection analysis (FIA) biosensor system was developed for the determination of the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). The system consisted of an enzyme column of pronase immobilized on activated arylamine glass beads and a L-amino acid oxidase electrode connected in series. The dipeptide bond of aspartame was cleaved by immobilized pronase to release phenylalanine, which was in turn monitored by the enzyme electrode that used L-amino acid oxidase immobilized on a preactivated nylon membrane in combination with an amperometric electrode (platinum vs silver/silver chloride, 700 mV). The response of the FIA biosensor was linear up to 1 mM aspartame with a lower detection limit of 25 microM and had good reproducibility (rsd 0.3%). The FIA biosensor was stable for at least 30 h of continuous use at Tr. Each assay takes 4 min giving a sample throughput of 15 h-1. When applied to aspartame in dietary food products the results obtained agreed well with those reported by the product manufacturers.

Aspartame↗
PubMed1992

Synthesis of a homologous series of ketomethylene arginyl pseudodipeptides and application to low molecular weight hirudin-like thrombin inhibitors.

The design of low molecular weight thrombin inhibitors IIa-d (hirutonins) that bind concurrently with the enzyme's catalytic site and auxiliary "anion-binding exosite" for fibrinogen recognition is reported. A practical synthesis of the required homologous ketomethylene arginyl dipeptide inserts [Arg psi CO(CH2)nCO] (n = 1-4) corresponding to the P1-P1' scissile position of hirutonins is described. The substitution of the scissile amide function by a ketomethylene group is compatible with the enzyme active site and conferred complete plasma proteolytic stability. This modification also enhanced enzyme affinity up to 20-fold with hirutonin-4 (IIb, n = 4) displaying highest affinity (Ki = 140 +/- 20 pM). Hirutonins 1-4 exhibited potent inhibition of plasma prothrombin time (PT) and activated partial thromboplastin time (aPTT). The inhibition was biphasic and showed good correlation with the corresponding Ki. Hirutonin-2 inhibited thrombin-mediated platelet aggregation and exhibited a strong antithrombotic effect comparable to r-hirudin in an in vivo rat arteriovenous shunt model (ED15 = 1.20 mg/kg for hirutonin-2 and 1.14 mg/kg for r-hirudin). Lower molecular weight inhibitors were obtained by substituting the six native amino acid residues (Q-S-H-N-D-G), connecting the active site and the auxiliary exosite binding elements with a variable number of interening omega-aminopentenoyl units. In addition, the exosite component was reduced to seven amino acid residues (D-F-E-P-I-P-L). Incorporation of these modifications into the bifunctional format resulted in nanomolar thrombin inhibitory peptides (IIIa-c). The resulting inhibitors were studied by molecular modeling with alpha-thrombin, and the bimolecular interactions served to explain the retention of high enzyme affinity.

Amino Acid Sequence↗
PubMed1991

A new class of potent thrombin inhibitors that incorporates a scissile pseudopeptide bond.

A synthetic hirudin peptide analog corresponding to N alpha-acetyl [D-Phe45, Arg psi(COCH2)47, Gly48]desulfo hirudin45-65 (P79) was synthesized. Comparative kinetic studies showed that while recombinant hirudin (HV2) is a slow-tight binding inhibitor, P79 behaves as a classical competitive inhibitor of human alpha-thrombin (Ki = 3.7 +/- 0.3 x 10(-10) M) and bovine alpha-thrombin (1.8 +/- 0.7 x 10(-9) M). P79 showed saturable inhibition of plasma APTT. The P1' subsite of P79 is isosteric with the glycine residue of the natural thrombin substrate fibrinogen, but is proteolytically stable due to the incorporation of a ketomethylene pseudopeptide bond. The model active site-directed tripeptide [D-Phe-Pro-Arg psi(COCH2)CH2COOCH3, P79L] corresponding to the amino terminal of P79 also binds competitively to the active site of alpha-thrombin and inhibited the proteolysis of a tripeptidyi substrate with a Ki = 17.9 +/- 2.1 microM (human) and 10.3 +/- 3.6 microM (bovine) alpha-thrombin. NMR experiments indicated that P79L and the corresponding amino terminal residues of P79 occupy a mutually exclusive binding site on bovine alpha-thrombin while the carboxyl terminal tail of the latter adopts a similar bound conformation as the fragment hirudin55-65 which is known to interact with the 'anion' exosite. Taken together these results provide conclusive evidence that the high antithrombin activity of N alpha-acetyl[D-Phe45, Arg psi(COCH2)47, Gly48]desulfo hirudin45-65 stems from the concurrent interaction with the catalytic site and the putative 'anion' exosite through its respective NH2- and COOH-terminal recognition sites.

Amino Acid Sequence↗
PubMed1991

Prevalence of illicit drug use among prenatal patients and predictive validity of nurses' judgments.

The purposes of this investigation were to: (1) estimate the prevalence of illicit drug use within the prenatal population of a midwestern suburban ambulatory care center; (2) explore the relationship between nurses' judgments of patient illicit drug use and urine toxicology results; and (3) determine if a difference exists between nurses' judgments of illicit drug use by private physicians' patients (PPP) and nurses' judgments of illicit drug use by resident physicians' patients (RPP). For a 16-week period, all new prenatal patients (N = 189) were included in this study; 78 (41%) were in the RPP group and 111 (59%) were in the PPP group. Urine remaining from routine urinalysis was assayed for seven drugs or drug classes. Fourteen (7.5%) subjects tested positive for illicit drugs, 8 (10.3%) in the RPP group, and 6 (5.4%) in the PPP group (chi 2, P greater than .33). Using a Likert-type scale, nurses rated the likelihood of a positive result of each patient's urine test. Nurses' judgments of patient illicit drug use and positive results were related, r = .28. Nurses were more likely (P less than .0001) to suspect residents' patients of illicit drug use than private physicians' patients.

Adult↗
PubMed1990

Bifunctional thrombin inhibitors based on the sequence of hirudin45-65.

The interaction of alpha-thrombin with the hirudin (HV1) fragment N alpha-acetyl desulfo hirudin45-65 (P51) was investigated. Kinetic analysis revealed that P51 inhibits the proteolysis of a tripeptidyl substrate with Ki = 0.72 +/- 0.13 and 0.11 +/- 0.03 microM for bovine and human alpha-thrombins, respectively. The inhibition was partially competitive, affecting substrate binding to the enzyme-inhibitor complex by a factor alpha = 2 (bovine) and alpha = 4 (human) characteristic of hyperbolic inhibitors. P51 also inhibited thrombin-induced fibrin clot formation with IC50 values of 0.94 +/- 0.20 and 0.058 +/- 0.006 microM for bovine and human alpha-thrombins, respectively. The enhanced antithrombin activity for human thrombin could be attributed to species variations in the putative auxiliary "anion" exosite since N alpha-acetyl desulfo hirudin55-65 displayed the same rank order of potency shift in a clotting assay without inhibiting the amidolytic activity of either enzyme. From these observations, a potent thrombin inhibitor was designed having modified residues corresponding to the P1 and P3 recognition sites. N alpha-Acetyl[D-Phe45, Arg47] hirudin45-65 (P53) emerged as a pure competitive inhibitor with a Ki = 2.8 +/- 0.9 nM and IC50 = 4.0 +/- 0.8 nM (human alpha-thrombin) and is designated as a "bifunctional" inhibitor. Its enhanced potency could be explained by a cooperative intramolecular interaction between the COOH-terminal domain of the inhibitor and the auxiliary exosite of thrombin on the one hand, and the modified NH2-terminal residues with the catalytic site on the other.

Amino Acid Sequence↗