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Biomedical subjects

T Hall

Publications and source records attributed to T Hall.

At least 19 recordsLinked to original sources

Fast electron transport in ultraintense laser pulse interaction with solid targets by rear-side self-radiation diagnostics.

We report on rear-side optical self-emission results from ultraintense laser pulse interactions with solid targets. A prompt emission associated with a narrow electron jet has been observed up to aluminum target thicknesses of 400 microm with a typical spreading half-angle of 17 degrees. The quantitative results on the emitted energy are consistent with models where the optical emission is due to transition radiation of electrons reaching the back surface of the target or due to a synchrotron-type radiation of electrons pulled back to the target. These models associated with transport simulation results give an indication of a temperature of a few hundred keV for the fast-electron population.

Journal Article↗

Equation of state data for iron at pressures beyond 10 Mbar.

We present equation of state points for iron, in the pressure range 10-45 Mbar, the first obtained with laser-driven shock waves. The experiment has been performed with the high energy laser Phebus, optically smoothed with Kinoform phase plates. Our results double the set of existing experimental data at very high pressures showing good agreement with the predictions of the quotidian equation of state model and with previous results.

Journal Article↗

A randomized clinical trial of manual therapy for cervico-brachial pain syndrome -- a pilot study.

Cervico-brachial pain syndrome is an upper quarter pain condition in which mechanosensitive neural tissue is considered a primary feature. A single-blind randomized controlled trial was conducted to determine the clinical effect of two manual therapy interventions. Thirty subjects (20 females and 10 males) were randomly allocated to one of three groups - one of two manual therapy intervention groups or a control group. One manual therapy intervention group consisted of passive techniques aimed at mobilizing neural tissue structures and the cervical spine. The other involved indirect manual therapy techniques with a focus on articular components of the gleno-humeral joint and thoracic spine. The treatment period lasted 8 weeks in total and was combined with a home exercise programme. Following the 8-week baseline period the control group were crossed over into the specific neural tissue manual therapy group. Pain visual analogue scale (VAS), the short-form McGill pain and Northwick Park neck pain questionnaires were completed before, midway and after the treatment period. The findings suggest that both manual physiotherapy interventions combined with home exercises are effective in improving pain intensity, pain quality scores and functional disability levels. A group difference was observed for the VAS scores at 8 weeks with the neural manual therapy technique having a significantly lower score.

Adult↗

Interferometric measurement of preheating in laser shocks.

We present a preliminary study of preheating in laser shocks using an interferometric diagnostic. A low energy probe laser divided in two by a biprism produces an interference pattern on the rear side of a target. The expansion due to preheating causes a fringe shift before shock arrival. A streak camera produces time-resolved images of the target rear side, which are filtered to reduce noise and correct for instrumental effects. Results are compared with an analytical model, which assumes that preheating is due to x rays, and with results from reflectivity measurements.

Journal Article↗

Normal and abnormal heme biosynthesis. 3.(1)Synthesis and metabolism of tripropionate analogues of coproporphyrinogen-III: novel probes for the active site of coproporphyrinogen oxidase.

Coproporphyrinogen oxidase (copro'gen oxidase) catalyses the oxidative decarboxylation of two propionate side chains on coproporphyrinogen-III to produce protoporphyrinogen-IX. This process is very poorly understood at a molecular level, and copro'gen oxidase remains one of the least well-characterized enzymes in the heme biosynthetic pathway. To provide a rigorous test for a proposed model for substrate recognition and binding by this enzyme, two tripropionate analogues of copro'gen-III were prepared where an ethyl group replaced one of the usual propionate residues on positions 13 or 17. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initially synthesized via tripyrrene and a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium-amalgam to give the unstable porphyrinogens needed for the biochemical investigations. The modified structure with a 13-ethyl moiety was metabolized by avian preparations of copro'gen oxidase to give a monovinylic product, but the isomeric 17-ethylporphyrinogen afforded a divinylic product, albeit with poorer overall conversion. These results strongly support the proposed model for substrate binding at the active site of copro'gen oxidase.

Binding Sites↗

Safety and immunogenicity of three lots of meningococcal serogroup C conjugate vaccine administered at 2, 3 and 4 months of age.

The reactogenicity and immunogenicity of meningococcal serogroup C conjugate (MenC) vaccine was assessed in 322 infants vaccinated at 2, 3, and 4 months of age, with concomitant administration of mixed diphtheria-tetanus-whole-cell pertussis vaccine and Haemophilus influenzae type b conjugate vaccine (DTwP-Hib) and oral polio vaccine. All infants in whom post-vaccination meningococcal C anticapsular IgG levels were assayed (n = 265) attained > or = 2 microg ml(-1). Serum bactericidal titres were assayed for a proportion of subjects (n = 171), 98% of whom obtained a reciprocal titres > or = 8. Local reactions were less frequent at the MenC injection site than at the DTP-Hib site. Systemic events were frequent, but consistent with established DTwP-Hib experience. The study demonstrates that MenC vaccine is immunogenic and well tolerated in infants at manufacturing scale production levels.

Antibodies, Bacterial↗

Use of low-density foams as pressure amplifiers in equation-of-state experiments with laser-driven shock waves.

The applicability of foams to equation of state experiments with laser-produced shocks has been studied. The pressure increase due to impedance mismatch at the payload-foam interface was measured experimentally using sub-ns laser pulses smoothed with phase zone plates. Foams of density in the range 5-900 mg/cm(3) and of thicknesses of 50-150 microm were used. A model has been developed to study pressure amplification and the conditions under which the shock is stationary. Two-step two-material targets, allowing simultaneous measurements of the shock velocities in the two materials, were then used to obtain relative equation of state data. Pressures higher than 100 Mbar were achieved in gold.

Journal Article↗

Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria.

After initial successful evaluation of the circumsporozoite-based vaccine RTS,S/SBAS2, developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research, protective efficacy of several regimens against Plasmodium falciparum challenge was determined. A controlled phase 1/2a study evaluated 1 or 2 standard doses of RTS,S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received standard, one-half, or one-fifth doses. RTS,S/SBAS2 was safe and immunogenic in all groups. Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge, malaria developed in 7 of 10 who received 1 dose, in 7 of 14 who received 2 doses, in 3 of 6 who received 3 standard doses, in 3 of 7 who received 3 one-half doses, in 3 of 4 who received 3 one-fifth doses, and in 22 of 23 control subjects. Overall protective efficacy of RTS,S/SBAS2 was 41% (95% confidence interval, 22%-56%; P=.0006). This and previous studies have shown that 2 or 3 doses of RTS,S/SBAS2 protect against challenge with P. falciparum sporozoites.

Adolescent↗

Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure.

OBJECTIVE: The possible molecular mimicry of the Epstein-Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B'/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3-1,025, P < 10(-11)). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53-infinity, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE. METHODS: We selected 196 antinuclear antibody-positive adult SLE patients (age > or =20 years) and 2 age-, race-, and sex-matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), or varicella-zoster virus (VZV) by standardized enzyme-linked immunosorbent assays. RESULTS: Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45-infinity, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV-2, or VZV. CONCLUSION: These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.

Adult↗

A Plasmodium falciparum protein located in Maurer's clefts underneath knobs and protein localization in association with Rhop-3 and SERA in the intracellular network of infected erythrocytes.

We report on the characterization of monoclonal antibodies against Plasmodium falciparum schizonts, which recognize parasite proteins of 130 kDa and 20 kDa. The 130-kDa protein was released by alkaline sodium carbonate treatment, suggesting that the protein is a peripheral membrane protein, while the 20-kDa protein remained associated with the membranes following alkali treatment, suggesting it may be an integral membrane protein. Both proteins were localized to large cytoplasmic vesicles within the cytoplasm of trophozoite and schizont-infected erythrocytes by immunofluorescence assay and confocal microscopy. Both proteins colocalized with Bodipy-ceramide in trophozoite and immature schizont-infected erythrocytes, but not in segmenters. The 130-kDa protein was localized by immunoelectron microscopy (IEM) to Maurer's clefts underneath knobs in a knobby and cytoadherent (K +/ C+) P. falciparum strain. No IEM reactivity was obtained in a knobless and non-cytoadherent (K-/C-)

Animals↗

Preterm delivery and the severity of violence during pregnancy.

OBJECTIVE: To determine the severity and consequences of physical violence during pregnancy among participants in a health department prenatal care coordination program. STUDY DESIGN: The prospective cohort study included all program participants from 1994 to 1996. Care coordinators screened participants for physical violence during pregnancy using a validated, systematic assessment protocol three times during prenatal care. The protocol was linked with prenatal records, delivery records and infant records to document complications and infant outcomes. Multiple logistic regression was used to assess the relationship between severe physical violence during pregnancy and pregnancy outcome while controlling for confounding factors. RESULTS: Among the 550 participants, 13.5% reported violence during pregnancy; it included 6.7% severe violence (hitting, kicking, injury with a weapon and abdominal injury) and 6.7% moderate violence (threats, slapping, shoving and sexual abuse). Severe physical prenatal violence was significantly associated with spontaneous preterm labor, preterm delivery, very preterm delivery, very low birth weight, preterm/low birth weight, mean birth weight, mean newborn hospital charges, five-minute Apgar < 7, neonatal intensive care unit admission, and fetal or neonatal death. Body site injured, timing of violence and number of violent incidents were significant factors associated with violence during pregnancy and preterm delivery. CONCLUSION: Because severe physical violence during pregnancy was a significant problem in this population, intervention programs are needed to reduce prenatal violence and its consequences.

Adolescent↗

Characterization of the recombinant IKK1/IKK2 heterodimer. Mechanisms regulating kinase activity.

Nuclear factor kappa B (NF-kappaB) is a ubiquitous, inducible transcription factor that regulates the initiation and progression of immune and inflammatory stress responses. NF-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkappaB, initiated by an IkappaB kinase (IKK) complex. This IKK complex includes a catalytic heterodimer composed of IkappaB kinase 1 (IKK1) and IkappaB kinase 2 (IKK2) as well as a regulatory adaptor subunit, NF-kappaB essential modulator. To better understand the role of IKKs in NF-kappaB activation, we have cloned, expressed, purified, and characterized the physiological isoform, the rhIKK1/rhIKK2 heterodimer. We compared its kinetic properties with those of the homodimers rhIKK1 and rhIKK2 and a constitutively active rhIKK2 (S177E, S181E) mutant. We demonstrate activation of these recombinantly expressed IKKs by phosphorylation during expression in a baculoviral system. The K(m) values for ATP and IkappaBalpha peptide for the rhIKK1/rhIKK2 heterodimer are 0.63 and 0.60 micrometer, respectively, which are comparable to those of the IKK2 homodimer. However, the purified rhIKK1/rhIKK2 heterodimer exhibits the highest catalytic efficiency (k(cat)/K(m)) of 47.50 h(-1) micrometer(-1) using an IkappaBalpha peptide substrate compared with any of the other IKK isoforms, including rhIKK2 (17.44 h(-1) micrometer(-1)), its mutant rhIKK2 (S177E, S181E, 1.18 h(-1) micrometer(-1)), or rhIKK1 (0.02 h(-1) micrometer(-1)). Kinetic analysis also indicates that, although both products of the kinase reaction, ADP and a phosphorylated IkappaBalpha peptide, exhibited competitive inhibitory kinetics, only ADP with the low K(i) of 0.77 micrometer may play a physiological role in regulation of the enzyme activity.

Catalysis↗

Escherichia coli beta-galactosidase is heterogeneous with respect to a requirement for magnesium.

Commercially obtained E. coli beta-galactosidase was stored at 25 degrees C in buffer containing 1 mM MgCl2 and in buffer containing no added MgCl2. Samples were removed at set times and the activity of individual enzyme molecules assayed. When stored in the presence of 1 mM magnesium, the number of active molecules did not change over a 2.5-h period. When stored in the absence of added MgCl2, over half the enzyme molecules became inactive within the first hour. However, those molecules which retained activity remained active for the duration of the experiment. This indicates that there may exist two populations of E. coli beta-galactosidase, one which requires storage in the presence of the higher concentration of Mg2+ in order to remain active. There was no observed correlation between this requirement for magnesium and reaction rate. Additionally, the presence of the 1 mM MgCl2 was found to decrease the average activity of the beta-galactosidase molecules under the conditions employed.

Bacterial Proteins↗

Latex allergy.

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Dermatitis, Allergic Contact↗

Newly induced beta-galactosidase molecules have a higher activity than the basally expressed enzyme.

OBJECTIVE: The objective of this study was to compare the activities of individual molecules of induced and basally expressed Escherichia coli beta-galactosidase. BACKGROUND DATA: Single-molecule assays of enzymes have determined that individual molecules are not identical. They differ with respect to catalytic rate. The structural cause and cellular role of this microheterogeneity is as yet unknown. METHODS: E. coli were grown and induced to produce beta-galactosidase by treatment with isopropyl-beta-D-thiogalactopyranoside. Cells were lysed and the beta-galactosidase assayed with capillary electrophoresis instrumentation utilizing post-column, laser-induced fluorescence detection. The enzyme obtained from treated cells were compared to that from untreated cells. RESULTS: The activity of newly induced beta-galactosidase was found to be approximately 20% greater than that of the basally expressed enzyme. This measured difference is statistically significant. CONCLUSIONS: Production of beta-galactosidase in E. coli under differing conditions results in differences in the activities of the individual enzyme molecules.

Electrophoresis, Capillary↗

Foam-induced smoothing studied through laser-driven shock waves

The influence of foams on the uniformity of laser energy deposition has been studied by measuring laser-driven shock waves breakout from foam-aluminum layered targets. Well characterized laser nonuniformities have been produced first by using phase zone plates to get a smooth beam and then by inserting different opaque grids before the foam. Smoothing has been studied as a function of foam density and grid materials (producing different radiative effects).

Journal Article↗

Experimental evidence of electric inhibition in fast electron penetration and of electric-field-limited fast electron transport in dense matter

Fast electron generation and propagation were studied in the interaction of a green laser with solids. The experiment, carried out with the LULI TW laser (350 fs, 15 J), used K(alpha) emission from buried fluorescent layers to measure electron transport. Results for conductors (Al) and insulators (plastic) are compared with simulations: in plastic, inhibition in the propagation of fast electrons is observed, due to electric fields which become the dominant factor in electron transport.

Journal Article↗

Simultaneous X-Ray and TeV Observations of a Rapid Flare from Markarian 421.

Mrk 421 was observed for about 2 days with BeppoSAX in 1998 April as part of a worldwide multiwavelength campaign. A large, well-defined flare was observed in X-rays. The same flare was observed simultaneously at TeV energies by the Whipple Observatory gamma-ray telescope. These data provide (1) the first evidence that the X-ray and TeV intensities are well correlated on timescales of hours and (2) the first exactly simultaneous X-ray and TeV spectra. The results imply that the X-ray and TeV photons derive from the same region and from the same population of relativistic electrons. The physical parameters deduced from a homogeneous synchrotron self-Compton model for the spectral energy distribution yield electron cooling times close to the observed variability timescales.

Journal Article↗