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Biomedical subjects

D Mack

Publications and source records attributed to D Mack.

At least 19 recordsLinked to original sources

Biofilm formation in medical device-related infection.

Medical device-associated infections, most frequently caused by coagulase-negative staphylococci, especially Staphylococcus epidermidis, are of increasing importance in modern medicine. Regularly, antimicrobial therapy fails without removal of the implanted device. The most important factor in the pathogenesis of medical device-associated staphylococcal infections is the formation of adherent, multilayered bacterial biofilms. There is urgent need for an increased understanding of the functional factors involved in biofilm formation, the regulation of their expression, and the interaction of those potential virulence factors in device related infection with the host. Significant progress has been made in recent years which may ultimately lead to new rational approaches for better preventive, therapeutic, and diagnostic measures.

Adhesins, Bacterial↗

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Journal Article↗

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

High mortality of infant bacteraemia clinically indistinguishable from severe malaria.

BACKGROUND: Early recognition of children at highest risk of dying and the targeting of appropriate drug therapy are vital to the improvement of paediatric care in developing countries. This will rely upon the development of simple clinically-based algorithms and treatment guidelines. AIM: To determine the role of bacteraemia in children presenting with clinical signs and symptoms of severe malaria. DESIGN: Retrospective analysis of blood culture results following prospective data collection. METHODS: We studied 251 children presenting with symptoms and signs of severe malaria to a tertiary referral centre in Ghana. Blood was taken for malaria blood films, bacterial culture and haemograms. RESULTS: On the basis of clinical signs alone, malaria-film-positive (n = 182) and -negative (n = 69) patients were indistinguishable. Some 40% of film-negative patients were bacteraemic, vs. 12% of film-positive patients. Severe malaria and bacteraemia were not positively associated. Film-negative bacteraemic patients had a mortality of 39%, primarily affecting the age group <30 months. DISCUSSION: Infants presenting with symptoms and signs of severe malaria but a negative malaria film require immediate antibiotic treatment.

Age Distribution↗

Celiac disease.

Explore the source record for details and available documents.

Adult↗

Delivery of antimicrobials into parasites.

To eliminate apicomplexan parasites, inhibitory compounds must cross host cell, parasitophorous vacuole, and parasite membranes and cyst walls, making delivery challenging. Here, we show that short oligomers of arginine enter Toxoplasma gondii tachyzoites and encysted bradyzoites. Triclosan, which inhibits enoyl-ACP reductase (ENR), conjugated to arginine oligomers enters extracellular tachyzoites, host cells, tachyzoites inside parasitophorous vacuoles within host cells, extracellular bradyzoites, and bradyzoites within cysts. We identify, clone, and sequence T. gondii enr and produce and characterize enzymatically active, recombinant ENR. This enzyme has the requisite amino acids to bind triclosan. Triclosan released after conjugation to octaarginine via a readily hydrolyzable ester linkage inhibits ENR activity, tachyzoites in vitro, and tachyzoites in mice. Delivery of an inhibitor to a microorganism via conjugation to octaarginine provides an approach to transporting antimicrobials and other small molecules to sequestered parasites, a model system to characterize transport across multiple membrane barriers and structures, a widely applicable paradigm for treatment of active and encysted apicomplexan and other infections, and a generic proof of principle for a mechanism of medicine delivery.

Amino Acid Sequence↗

Measurements of GnE/GnM from the 2H(e-->,en-->)1H Reaction to Q2=1.45 (GeV/c)2.

We report new measurements of the ratio of the electric form factor to the magnetic form factor of the neutron, G(n)(E)/G(n)(M), obtained via recoil polarimetry from the quasielastic 2H(e-->,e(')n-->)1H reaction at Q2 values of 0.45, 1.13, and 1.45 (GeV/c)(2) with relative statistical uncertainties of 7.6% and 8.4% at the two higher Q2 points, which points have never been achieved in polarization measurements.

Journal Article↗

Cross-section measurement of charged-pion photoproduction from hydrogen and deuterium.

We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90 degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). The data at E(gamma) greater, similar 3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.

Journal Article↗

High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.

High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.

Journal Article↗

Longitudinal electroproduction of charged pions from (1)H, (2)H, and (3)He.

Separated longitudinal and transverse cross sections for charged pion electroproduction from (1)H, (2)H, and (3)He were measured at Q(2) = 0.4 (GeV/c)(2) for two values of the invariant mass, W = 1.15 GeV and W = 1.60 GeV, in a search for a mass dependence which would signal the effect of nuclear pions. This is the first such study that includes recoil momenta significantly above the Fermi surface. The longitudinal cross section, if dominated by the pion-pole process, should be sensitive to nuclear pion currents. Comparisons of the longitudinal cross section target ratios to a quasifree calculation reveal a significant suppression in (3)He at W = 1.60 GeV. The W = 1.15 GeV results are consistent with simple estimates of the effect of nuclear pion currents, but are also consistent with pure quasifree production.

Journal Article↗

Measurement of the electric form factor of the neutron through d-->(e-->,e(')n)p at Q2 = 0.5 (GeV/c)(2).

We report the first measurement using a solid polarized target of the neutron electric form factor G(n)(E) via d-->(e-->,e(')n)p. G(n)(E) was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia ( 15ND3). The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility in quasifree kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find G(n)(E) = 0.04632+/-0.00616(stat)+/-0.00341(syst) at Q2 = 0.495 (GeV/c)(2).

Journal Article↗

Fusion AML1 transcript in a radiation-associated leukemia results in a truncated inhibitory AML1 protein.

AML1 is a transcription factor that is essential for normal hematopoietic development. It is the most frequent target for translocations in acute leukemia. Recently, fluorescence in situ hybridization was used to identify a novel syndrome of radiation-associated secondary acute myelogenous leukemia that had AML1 translocations. Using polymerase chain reaction, the AML1 fusion transcript was isolated from the patient who had a t(19;21) radiation-associated leukemia. The AML1 gene is fused out of frame to chromosome 19 sequences, resulting in a truncated AML protein bearing the DNA binding domain but not the transcriptional activation domain. This fusion AML1 protein functions as an inhibitor of the normal AML1 protein. (Blood. 2001;97:2168-2170)

Acute Disease↗

Correlation of biofilm expression types of Staphylococcus epidermidis with polysaccharide intercellular adhesin synthesis: evidence for involvement of icaADBC genotype-independent factors.

IcaADBC-encoded proteins mediate synthesis of the intercellular polysaccharide adhesin (PIA), which is essentially involved in Staphylococcus epidermidis biofilm formation. Seventy S. epidermidis isolates were investigated for their ability to form biofilm and synthesize PIA in different growth media including trypticase soy broth obtained from Becton Dickinson (TSBBBL), or Oxoid (TSB(OXOID)), and TSB(OXOID) supplemented with 0.5% N-acetylglucosamine, and for the presence of icaADBC. Dependent on the medium used (TSB(BBL) or TSB(OXOID)), the isolates exhibited a differential expression of PIA and biofilm formation, with 51 (72.85%) and 34 (48.57%) being biofilm positive, respectively. Using these growth media four different expression phenotypes were differentiated: similar quantities of biofilm formation in both TSBBBL and TSB(OXOID) (11 isolates, type A), significantly reduced biofilm expression in TSB(OXOID) compared to TSB(BBL) (23 isolates, type B), biofilm negative in TSB(OXOID) but biofilm producing in TSB(BBL) (17 isolates, type C) and biofilm negative in both media (19 isolates, type D). For all strains a biofilm-positive phenotype in a specific medium was closely linked to expression of PIA in that medium. All but one strain of expression type A-C and 7/19 expression type D strains were icaADBC positive. On the basis of restriction fragment length polymorphisms, the isolates were classified into two main icaADBC genotypes. There was no association between the observed biofilm-expression types and a defined icaADBC genotype. In the biofilm-negative S. epidermidis 5179, isolated from a ventriculo-atrial shunt infection, the insertion of IS257 interrupted the transcription of icaADBC, resulting in a PIA- and biofilm-negative phenotype. In all other icaADBC-positive, biofilm-negative isolates no major alterations of the icaADBC gene locus were identified. Obviously, expression of icaADBC, PIA synthesis and biofilm formation are integrated into a complex regulatory network involving other determinants independent of icaADBC genotype. Inactivation of icaADBC by IS elements is apparently a rare cause of a biofilm-negative phenotype in clinical S. epidermidis isolates.

Bacterial Proteins↗

Effective long-term androgen suppression in men with prostate cancer using a hydrogel implant with the GnRH agonist histrelin.

OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing testosterone production in men with prostate cancer and to determine the effective dose (one, two, or four implants). METHODS: Forty-two men with prostate cancer and indications for androgen ablation were treated with one, two, or four implants. In two of the clinics, comprising 27 subjects, the treatment period was 12 months, with replacement with the same number of implants at 12-month intervals. In a third clinic, which treated 15 subjects, the implants were left in place for up to 30 months. The total experience was 605 treatment months. RESULTS: The histrelin levels were detected in serum proportional to the number of implants placed. The response, however, was similar among all three dose levels, with testosterone and luteinizing hormone essentially completely suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93 +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6 months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38 assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks of the initial implant placement. All patients followed for up for 12 months after placement of the initial set of implants maintained suppression of testosterone production while the implant was in place. CONCLUSIONS: The histrelin hydrogel implant provided adequate and reliable delivery of the potent GnRH agonist histrelin during at least 1 year using a single implant in men with prostate cancer. No apparent advantages were found in using more than one implant, and the question of the possible effectiveness of even lower doses remains open. This treatment modality appears to be both safe and effective.

Aged↗