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Biomedical subjects

D Hudson

Publications and source records attributed to D Hudson.

At least 19 recordsLinked to original sources
PubMed2006

Prevention oriented epidemiologic study of accidental burns in rural areas of Ardabil, Iran.

PURPOSE OF STUDY: Burns are one of the leading causes of injury-related deaths in Iran. We conducted a study to investigate features of burns in rural areas of Ardabil Province from October 2004 through March 2005, with an aim to providing content for effective prevention programs. BASIC PROCEDURES: This study employed longitudinal prospective methodology. The study population included all patients presenting with burns to local health care facilities during the study period. MAIN FINDINGS: A total of 1179 cases were studied. Most of the cases (59.4%) were females. Mean of age of victims was 22.3+/-19 years in females and 13.6+/-17 years in males. The vast majority (91.2%) of burns occurred at home. More than two-thirds of burns were because of hot liquids or steam. The majority of scald burns resulted during use of heating devices such as samovars, gas stoves, valors and picnic gas stoves. Overturning and spilling of hot liquids were the most common injury mechanisms. PRINCIPLE CONCLUSIONS: Prevention programs should focus on children and adult women. Prevention efforts should target home environments and focus on prevention of scalding burns.

Accidents, Home↗
PubMed2006

The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth.

The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.

Androgens↗
PubMed2004

Field investigation into unsaturated flow and transport in a fault: model analyses.

Results of a fault test performed in the unsaturated zone of Yucca Mountain, Nevada, were analyzed using a three-dimensional numerical model. The fault was explicitly represented as a discrete feature and the surrounding rock was treated as a dual-continuum (fracture-matrix) system. Model calibration against seepage and water-travel-velocity data suggests that lithophysal cavities connected to fractures can considerably enhance the effective fracture porosity and therefore retard water flow in fractures. Comparisons between simulation results and tracer concentration data also indicate that matrix diffusion is an important mechanism for solute transport in unsaturated fractured rock. We found that an increased fault-matrix and fracture-matrix interface areas were needed to match the observed tracer data, which is consistent with previous studies. The study results suggest that the current site-scale model for the unsaturated zone of Yucca Mountain may underestimate radionuclide transport time within the unsaturated zone, because an increased fracture-matrix interface area and the increased effective fracture porosity arising from lithophysal cavities are not considered in the current site-scale model.

Biological Transport↗
PubMed2004

Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians.

Genome-wide scans were conducted for tuberculosis and leprosy per se in Brazil. At stage 1, 405 markers (10 cM map) were typed in 16 (178 individuals) tuberculosis and 21 (173 individuals) leprosy families. Nonparametric multipoint analysis detected 8 and 9 chromosomal regions respectively with provisional evidence (P<0.05) for linkage. At stage 2, 58 markers from positive regions were typed in a second set of 22 (176 individuals) tuberculosis families, with 22 additional markers typed in all families; 42 positive markers in 50 (192 individuals) new leprosy families, and 30 additional markers in all families. Three regions (10q26.13, 11q12.3, 20p12.1) retained suggestive evidence (peak LOD scores 1.31, 1.85, 1.78; P=0.007, 0.0018, 0.0021) for linkage to tuberculosis, 3 regions (6p21.32, 17q22, 20p13) to leprosy (HLA-DQA, 3.23, P=5.8 x 10(-5); D17S1868, 2.38, P=0.0005; D20S889, 1.51, P=0.004). The peak at D20S889 for leprosy is 3.5 Mb distal to that reported at D20S115 for leprosy in India. (151 words).

Brazil↗
PubMed2003

Multidipole analysis of simulated epileptic spikes with real background activity.

This simulated magnetoencephalographic study was designed to determine the variability in source parameters with real subject background activity when applying multidipole spatial-temporal dipole analyses, for which the correct model was compared with undermodeled and overmodeled cases. The simulated sources were created from patches of the cortical surface of each subject's MRI. One- and two-source frontal lobe spikes were generated in two cortical regions seen commonly in frontal lobe epilepsy patients tested at our site (orbital frontal and premotor cortex). In general, the modeling results were adequate for the correct model order and the correct model order plus one. In addition, if the localization error was less than 10 mm from the simulated source, the peak latency of the spike and orientation were very reliable, but the peak amplitude was not. The additional source in the overmodeled condition, on the other hand, was not localized reliably across the different epochs within subjects. The results suggest that consistency of the spike localization and inconsistency of other sources will allow one to determine reliably the appropriate model order in real data, and therefore determine single and multifocal spike generators.

Action Potentials↗
PubMed2002

Predictions of extreme precipitation and sea-level rise under climate change.

Two aspects of global climate change are particularly relevant to river and coastal flooding: changes in extreme precipitation and changes in sea level. In this paper we summarize the relevant findings of the IPCC Third Assessment Report and illustrate some of the common results found by the current generation of coupled atmosphere-ocean general circulation models (AOGCMs), using the Hadley Centre models. Projections of changes in extreme precipitation, sea-level rise and storm surges affecting the UK will be shown from the Hadley Centre regional models and the Proudman Oceanographic Laboratory storm-surge model. A common finding from AOGCMs is that in a warmer climate the intensity of precipitation will increase due to a more intense hydrological cycle. This leads to reduced return periods (i.e. more frequent occurrences) of extreme precipitation in many locations. The Hadley Centre regional model simulates reduced return periods of extreme precipitation in a number of flood-sensitive areas of the UK. In addition, simulated changes in storminess and a rise in average sea level around the UK lead to reduced return periods of extreme high coastal water events. The confidence in all these results is limited by poor spatial resolution in global coupled models and by uncertainties in the physical processes in both global and regional models, and is specific to the climate change scenario used.

Altitude↗
PubMed2000

Paralysis of the marginal mandibular branch of the facial nerve: treatment options.

Isolated paralysis of the marginal mandibular branch of the facial nerve results in an asymmetrical smile with elevation of the lower lip on the affected side. We discuss the surgical options for its correction and present a series of 26 patients who underwent either botulinum toxin injection, anterior belly of digastric transfer or free extensor digitorum brevis transfer as treatment. Botulinum toxin injection provided satisfactory results although these were temporary. Anterior belly of digastric transfer was the surgical procedure of choice. It yielded superior cosmetic results, less donor-site morbidity and required a shorter operating time. In more complex congenital facial hypoplastic syndromes, or following extensive surgery in the digastric triangle, the anterior belly of the digastric muscle may be absent or damaged. Extensor digitorum brevis transfer is the preferred option in these cases.

Adolescent↗
PubMed1999

Isolation and characterization of human monoclonal antibodies to digoxin.

Fab preparations of sheep polyclonal anti-digoxin Abs have proven useful for reversal of the toxic effects of digoxin overdoses in patients. Unfortunately, the use of foreign species proteins in humans is limited because of the potential for immunological responses that include hypersensitivity reactions and acute anaphylaxis. Immunization of recently developed transgenic mice, whose endogenous micro heavy and kappa light chain Ig genes are inactivated and which carry human Ig gene segments, with a digoxin-protein conjugate has enabled us to generate and isolate eight hybridoma cell lines secreting human sequence anti-digoxin mAbs. Six of the mAbs have been partially characterized and shown to have high specificity and low nanomolar affinities for digoxin. In addition, detailed competition binding studies performed with three of these mAbs have shown them to have distinct differences in their digoxin binding, and that all three structural moieties of the drug, the primary digitoxose sugar, steroid, and five-member unsaturated lactone ring, contribute to Ab recognition.

Animals↗
PubMed1999

A phosphate bound universal linker for DNA synthesis.

A uridine-based linker immobilized onto polystyrene beads at the 5' terminus via a phosphodiester group and then used as a universal DNA synthesis support gives post synthesis DNA cleavage in 8 hrs or less without alkali metal salts. DNA produced with the new support was analyzed by HPLC, MALDI mass spectroscopy and PAGE. Each analysis showed DNA of equivalent quality to that produced with standard CPG supports, without contaminating materials resulting from linker or support backbone decomposition.

Chromatography, High Pressure Liquid↗
PubMed1996

A new universal linker for solid phase DNA synthesis.

A method is described as an alternative to the use of nucleoside pre-functionalized supports for DNA synthesis. The procedure should allow the generation of 3'-OH terminal moieties of any natural or modified DNA fragment using a single derivatized solid support material. The method utilizes 1-O-(4,4' dimethoxytrityl)-2- O-succinoyl-3-N-allyloxycarbonylpropane immobilized on amino-propyl CPG followed by subsequent coupling of unit phosphoramidites. Work up is accomplished by removal of the 3-N-allyloxycarbonyl group [Pd(0) at 50 degrees C for 15 min] followed by cleavage under very mild conditions (aqueous TEAA/NH3 buffer pH 10, room temperature) to release the desired product. The mechanism is believed to involve nucleophilic attack of the linker-derived amino group on the 3'-phosphate triester, followed by elimination of the desired product. DNA synthesis with the new support and with classical nucleotide synthesis supports have been performed, and the products shown to be identical. Further proof of product integrity was given by MALDI mass spectral studies and the efficacy of DNA primers made with the new support in PCR amplification.

Allyl Compounds↗
PubMed1994

A humanized antibody specific for the platelet integrin gpIIb/IIIa.

C4G1, a murine mAb reactive with the platelet gpIIb/IIIa integrin, was humanized for potential treatment of thrombosis-related disorders. The variable regions of light- and heavy-chain cDNAs from the C4G1 hybridoma were first cloned and sequenced. Humanized C4G1 Ab of the IgG1 isotype was constructed by combining the complementarity-determining regions of C4G1 with human framework and constant regions. The human framework was chosen to maximize homology with the C4G1 variable region sequence, and a computer model of C4G1 was used to aid design of the final framework sequence. Genetic constructs were also developed to produce Fab and F(ab')2 fragments of the humanized C4G1 Ab. The humanized IgG1 Ab as well as the Fab and F(ab')2 fragments showed equivalent binding affinities to their murine counterparts, indicating no loss in binding affinity during the humanization process. The humanized Ab and its fragments were also shown to inhibit platelet aggregation and to inhibit binding of fibrinogen to gpIIb/IIIa in vitro.

Amino Acid Sequence↗
PubMed1994

Cytotoxicity of recombinant Fab and Fv immunotoxins on adult T-cell leukemia lymph node and blood cells in the presence of soluble interleukin-2 receptor.

Single-chain immunotoxins anti-Tac(Fv)-PE40 and anti-Tac(Fv)-PE40KDEL, composed of variable domains of the anti-Tac monoclonal antibody and truncated forms of Pseudomonas exotoxin, have shown potent cytotoxic activity against malignant peripheral blood mononuclear cells (PBMCs) from adult T-cell leukemia (ATL) patients originating from the Caribbean. However, several clinically important issues have not previously been addressed. These include the potential of soluble interleukin 2 receptor in ATL patients to block immunotoxin effectiveness, the relative sensitivity of malignant lymph node cells (LNCs) versus PBMCs, the effect of an immunotoxin with a prolonged half-life, and finally whether ATL cells from patients in Japan have toxin sensitivity equal to those of the Caribbean patients. To resolve these questions, we studied 32 malignant PBMC and LNC samples from 30 ATL patients from Japan. PBMCs from 27 of 27 patients were very sensitive with 50% inhibition of protein synthesis achieved with 0.02-0.85 ng/ml (0.3-13 pM) of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fv)-PE40. LNCs had sensitivity very similar to that of PBMCs in the five patients tested. The fully recombinant immunotoxin, anti-Tac(Fab)-PE40, which has 8-10 times the t1/2 alpha and beta compared to the Fv-immunotoxins, was also very cytotoxic toward cells from 27 of 27 patients tested with 50% inhibition of protein synthesis of 0.08-25 ng/ml. It was found that purified soluble interleukin 2 receptor added to the cytotoxicity assay decreased the cytotoxic activity of anti-Tac(Fv)-PE40KDEL or anti-Tac(Fab)-PE40, but that 1 x 10(4) units/ml or less had minimal competitive effects. It was found that ATL patients who have responded even incompletely to conventional chemotherapy have soluble interleukin 2 receptor levels lower than this at posttreatment. We conclude that recombinant immunotoxins containing anti-Tac(Fv) are effective against Japanese ATL PBMCs or LNCs and might be most effective if used in vivo after conventional chemotherapy. If it is found in humans that the effectiveness of single-chain recombinant toxins is limited by short half-life, anti-Tac(Fab)-PE40 should be considered as an alternative agent.

ADP Ribose Transferases↗