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Biomedical subjects

N Turner

Publications and source records attributed to N Turner.

At least 19 recordsLinked to original sources
PubMed2001

Designing a safer workplace: importance of job autonomy, communication quality, and supportive supervisors.

The direct and indirect effects of work characteristics on self-reported safe working were investigated in a longitudinal study of frontline manufacturing employees (N = 161). The work characteristics included job autonomy, role overload, role conflict, supportive supervision, training adequacy, job security, and communication quality. Job autonomy and communication quality were positively associated with safe working after prior levels of these variables were controlled for, and supportive supervision had a lagged positive effect on safe working 18 months later. Additional analyses showed that organizational commitment fully mediated the effect of job autonomy on safe working and partially mediated the effect of communication quality on safe working. The study suggests that work characteristics are important antecedents of safe working.

Adult↗
PubMed2000

Experiments on radiative collapse in laser-produced plasmas relevant to astrophysical jets

We report a laser experiment of astrophysical interest on radiative jet formation. Conically shaped targets are irradiated by intense laser light. An ablated plasma flow collides at the axis of the cone targets, then propagates at high Mach number, forming a jetlike structure. We measure time-resolved x-ray self-emission images from the jets. The diameter of the jet increases with decreasing atomic number of the irradiated target, suggesting that the collimation is due to radiative cooling. Two-dimensional simulations reproduce essential features of the experimental results.

Journal Article↗
PubMed2000

Chi-squared test.

Explore the source record for details and available documents.

Chi-Square Distribution↗
PubMed1999

Diffusion characteristics of calcium alginate gels.

The diffusivity of a protein solute (bovine serum albumin) within calcium alginate gels made from sodium alginate of different guluronic acid content was determined. It was found that protein diffusion within alginate gels, prepared to be isotropic in structure, was greatest for gels prepared from sodium alginate of low guluronic acid content as opposed to those prepared from sodium alginate of high guluronic acid content. This finding was explained in terms of the difference in flexibility of the polymer backbone of the two alginates. The greater the polymer backbone flexibility, the greater the solute diffusivity within the gel.

Alginates↗
PubMed1999

Uptake of postnatal services for mothers of newborn babies up to eight weeks of age.

AIM: Significant changes have occurred in the way postnatal care is funded in New Zealand since July 1996. This study investigated three aspects of postnatal care: the uptake of the six-week check, the six-week immunisation and breast feeding rates. METHOD: A prospective prevalence survey of 504 mothers of newborn babies recruited from birthing centres in urban Auckland over the period November 1997 to February 1998. A postal questionnaire was sent at ten weeks postnatal, covering issues concerning the six-week check, six-week immunisation and breast feeding. RESULTS: Four hundred and four completed questionnaires were obtained (82%); 98% of respondents had obtained a six-week check and 90% a six-week immunisation for their infant. Infants who received their six-week check from a general practitioner were more likely to be immunised. Younger mothers (15-19 years) and older mothers (35 years plus) were less likely to have immunised children. Of reasons given for not immunising, 43% were concerns over immaturity of the baby and 27% because the child was not well. At birth, 88% of mothers were fully breast feeding and 62% at six-weeks postnatal. Of the reasons given for stopping feeding, 41% stated insufficient milk or poor weight gain and 15% stated failure to establish feeding. CONCLUSIONS: Removing the six- week check from a general practitioner check and splitting it from the immunisation, has a deleterious effect on immunisation uptake. Mothers, particularly under 20 years, but also 35 years plus, are less likely to have immunised infants. A significant number of unimmunised babies arose from concerns that the baby may be too immature. The rate of breast feeding in New Zealand is continuing to drop. Actual rates fall well below mothers' desires to breast feed. Reasons given for stopping breast feeding point to a general need for greater postnatal support. The high rate of failure to establish feeding raises concerns over lack of early postnatal support. In July 1996 significant changes in payment of the maternity services benefit were introduced in New Zealand. In particular, postnatal services previously paid on a 'fee-for-service' basis were altered to a set capped amount for the 'postnatal module'. This led to concerns that care in the postnatal period had become more limited. In particular, there were anecdotal reports of the six-week check not being given, or being given by a range of providers who did not necessarily offer the opportunity for immunisation at the time of the check. Recent concerns have also been expressed about the apparent dropping immunisation rates in New Zealand, and the dropping breast feeding rates. The present study, developed in response to these concerns investigated three aspects of postnatal care: (a) The incidence of the uptake of the six-week check and whether mothers perceived any barriers to access. (b) The incidence of the uptake of the six-week immunisation and whether mothers perceived any barriers to access. (c) The rate of breast feeding and what barriers mothers perceived to continuing to breast feed.

Adolescent↗
PubMed1999

Bat rabies in South Carolina, 1970-90.

This retrospective study examines the geographic and temporal distribution of bat species submitted for rabies testing in South Carolina (USA) from 1970 to 1990. Histories of human or animal exposures to rabid and nonrabid bats submitted during this time period were compared. Two hundred and thirty-one bats were found to be rabid from the 2,657 bats submitted over this 20 yr period. The two species most frequently submitted for testing were Lasiurus borealis with 785 specimens (30% of the total) and Nycticeius humeralis with 607 specimens (22% of the total). Lasiurus borealis also had the highest prevalence of rabies (18%) while N. humeralis had the lowest prevalence (3%). Fifty-one percent (1,259) of the bats received for testing were submitted from June through August. The majority (54%) of rabid bats were received from August through October.

Animals↗
PubMed1998

Comparative intravenous toxicity of cisplatin solution and cisplatin encapsulated in long-circulating, pegylated liposomes in cynomolgus monkeys.

The toxicity of cisplatin encapsulated in pegylated, long-circulating liposomes (SPI-077) was compared with nonliposomal cisplatin in male and female cynomolgus monkeys (n = 2-4 per sex per group) treated with intravenous infusions of 2.5 or 25 mg/kg SPI-077, 2.5 mg/kg cisplatin, placebo liposomes, or saline once every 3 weeks for total of five treatments. All animals survived until scheduled necropsy at 3 days after the final treatment or after a treatment-free 4-week recovery period. Emesis occurred after each treatment in all cisplatin-treated monkeys, but only once in one monkey treated with high-dose SPI-077. Dose-related mild decreases in red blood cell (RBC) count, hemoglobin, and hematocrit to or slightly below low normal range occurred in the high-dose SPI-077 and placebo liposome treatment groups after each treatment, with partial to complete recovery between treatments and no signs of correlating bone marrow toxicity. Decreases were similar in cisplatin-treated monkeys, but resolved only slightly between treatments and after the end of treatment (continuing to decrease in females) and were accompanied by bone marrow hypocellularity. Indirect, but not direct, bilirubin levels were cyclically elevated in the high-dose SPI-077 and placebo-treated animals, but not in the other treatment groups. Levels had either fully resolved or were near baseline and/or saline group values prior to the next treatment. Serum cholesterol levels were cyclically increased in SPI-077- and placebo liposome-treated animals, and minimally increased numbers of foam cells were seen in the liver, spleen, kidney, and other organs; both were considered related to the lipid dose administered. Cisplatin-treated monkeys exhibited sensory polyneuropathy and moderate irreversible toxic tubular nephrosis, but no neuropathy or nephrotoxicity was seen in either SPI-077 treatment group. Microscopically, treatment-related cell death was seen in dorsal root ganglia (DRG), affecting 15% of the cells in cisplatin-treated animals, compared to 8 and 12% in the low- and high-dose SPI-077 treatment groups. Neither drug was ototoxic. In summary, repeated administration of SPI-077 produced minimal, reversible effects related to the lipid dose administered, mostly limited to the 25 mg/kg dose group. The most notable effects in this group were cyclical decreases in hematology parameters thought to be related to increased recycling of a small fraction of RBCs and limited cell death in the DRG in the absence of any neurophysiological changes. Animals treated with a 10-fold lower dose of cisplatin (2.5 mg/kg), in contrast, exhibited myelo-, nephro-, and neurotoxicity, including sensory neuropathy, and were emetic after every dose. The SPI-077 liposomal formulation of cisplatin may provide a less toxic alternative to standard cisplatin solution.

Animals↗
PubMed1998

Recombinant alpha-chains of type IV collagen demonstrate that the amino terminal of the Goodpasture autoantigen is crucial for antibody recognition.

Goodpasture's disease, an autoimmune disorder causing severe glomerulonephritis and pulmonary haemorrhage, is characterized by antibodies to the glomerular basement membrane (GBM). The principal target antigen has been identified as the carboxyl terminal non-collagenous (NC1) domain of the alpha3-chain of type IV collagen. Anti-GBM antibodies appear to recognize one major epitope that is common to all patients, and is largely conformational. We have analysed antibody binding to recombinant alpha(IV)NC1 domains using a construct and expression system shown to produce correctly folded antigen that is strongly recognized by autoantibodies. In this system, as with the native antigen, alpha3(IV)NC1 was bound strongly by antibodies from all patients, whereas the closely related alpha1(IV) and alpha5(IV)NC1 domains, similarly expressed, showed no such binding. A series of chimeric NC1 domains, between human alpha3(IV) and alpha1(IV), and between human and rat alpha3(IV), were expressed as recombinant molecules, and were recognized by autoantibodies to varying degrees. Strong binding required the presence of human alpha3(IV) sequence in the amino terminal region of both sets of chimeric molecules. This work strongly suggests that the amino terminal of alpha3(IV)NC1 is critical for antibody recognition, whereas the carboxyl terminal end of alpha3(IV)NC1 has a less important role.

Animals↗
PubMed1997

Characterization of the interaction between the Staphylococcus aureus clumping factor (ClfA) and fibrinogen.

The ability of Staphylococcus aureus to adhere to adsorbed fibrinogen and fibrin is believed to be an important step in the initiation of biomaterial and wound-associated infections. In this study, we show that the binding site in fibrinogen for the recently identified S. aureus fibrinogen-binding protein clumping factor (ClfA) is within the C-terminus of the fibrinogen gamma chain. S. aureus Newman cells expressing ClfA adhered to microtitre wells coated with recombinant fibrinogen purified from BHK cells, but did not adhere to wells coated with a purified recombinant fibrinogen variant where the 4 C-terminal residues of the gamma chain were replaced by 20 unrelated residues. In addition, a synthetic peptide corresponding to the 17 C-terminal amino acids of the fibrinogen gamma chain effectively inhibited adherence of ClfA-expressing cells to fibrinogen. In western ligand blots, a recombinant truncated ClfA protein called Clf33 (residues 221-550) recognized intact recombinant fibrinogen gamma chains, but failed to recognize recombinant fibrinogen gamma chains where the 4 C-terminal amino acids were altered by deletion or substitution. Previous studies have shown that the C-terminal domain of fibrinogen gamma chains contains a binding site for the integrin alphaIIb beta3 (glycoprotein gpIIb/IIIa) receptor on platelets [Kloczewiak, M., Timmons, S., Bednarek, M. A., Sakon, M. & Hawiger, J. (1989) Biochemistry 28, 2915-1919; Farrell, D. H., Thiagarajan, P., Chung, D. W. & Davie, E. W. (1992) Proc. Natl. Acad. Sci. USA 89, 10729-10732; Hettasch, J. M., Bolyard, M. G. & Lord, S. T. (1992) Thromb. Haemostasis 68, 701-706]. We now show that Clf33 inhibits ADP-induced, fibrinogen-dependent platelet aggregation in a concentration-dependent manner and inhibits adhesion of platelets to immobilized fibrinogen under fluid shear stress, indicating that the binding sites for the platelet integrin and the staphylococcal adhesin overlap. The interaction between Clf33 and fibrinogen was further characterized using the BIAcore biosensor. When soluble Clf33 was allowed to bind to immobilized fibrinogen, a Kd of 0.51 +/- 0.19 microM was experimentally determined using equilibrium binding data. It was also shown that the synthetic C-terminal gamma-chain peptide effectively inhibited this interaction.

Adenosine Diphosphate↗
PubMed1997

Large scale manufacturing of TXU(anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate for clinical trials.

We have conjugated the murine monoclonal anti-CD7 antibody TXU to the plant hemitoxin pokeweed antiviral protein (PAP) to construct an effective immunotoxin against CD7 antigen positive hematologic malignancies. The scaled-up production and purification of TXU antibody, PAP toxin, and TXU-PAP immunotoxin permitted the manufacturing of a highly purified clinical-grade TXU-PAP preparation. In clonogenic assays, TXU-PAP elicited selective and potent cytotoxicity against CD7 antigen positive human leukemia cells and killed primary clonogenic leukemic cells from T-lineage acute lymphoblastic leukemia (ALL) patients. To our knowledge, this pre-IND work represents the first effort of producing a clinical-grade PAP immunotoxin for treatment of T-lineage ALL. Since the CD7 antigen is also expressed on AML cells, TXU-PAP could also be useful for the treatment of CD7 positive acute myeloid leukemia (AML) patients.

Antibodies, Monoclonal↗
PubMed1996

A single-chain Fv reactive with the Goodpasture antigen.

Goodpasture's disease is defined by the presence of autoantibodies to the glomerular basement membrane and characterized clinically by rapidly progressive glomerulonephritis and pulmonary hemorrhage. P1, a murine monoclonal antibody to the Goodpasture antigen (the noncollagenous domain of the alpha 3 chain of type IV collagen, alpha 3(IV)NC1), has been a valuable reagent in investigating the pathogenesis of this disorder. The purpose of this study was to generate and characterize a recombinant form of P1 as a single-chain Fv (scFv). First strand cDNA was made from RNA extracted from the P1 hybridoma cell line, and DNA encoding the antibody light and heavy chain variable domains was amplified by polymerase chain reaction, using universal oligonucleotides. The purified products were ligated sequentially into an expression plasmid separated by a sequence encoding a 15 amino acid flexible oligopeptide linker. The resulting scFv was expressed in E. coli. Functional scFv, designated HBR-3, was obtained by denaturing and refolding the expressed product. HBR-3 was shown by ELISA, immunoblotting, and immunohistologic techniques, to have the same specificity for alpha 3(IV)NC1 as P1 and autoantibodies from patients with Goodpasture's disease. HBR-3 and P1 were shown to have similar affinity for their mutual ligand. On sections of normal human kidney, the scFv bound only to glomerular basement membrane and distal tubular basement membrane. It did not bind to the glomerular basement membrane of patients with Alport's syndrome, in whom the Goodpasture antigen is often not expressed in an antigenic form. We have, therefore, generated a scFv which reproduces the specific binding properties of the parent monoclonal antibody, P1. The potential of HBR-3 as a diagnostic reagent in Alport's syndrome has been demonstrated. The development of this recombinant molecule should permit new approaches to the investigation of Goodpasture's disease.

Amino Acid Sequence↗