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Biomedical subjects

A L Jones

Publications and source records attributed to A L Jones.

At least 37 records · Page 2Linked to original sources

Preliminary results and complications following limited open reduction and percutaneous screw fixation of displaced fractures of the acetabulum.

Twenty-four patients underwent attempted closed or limited open reduction of displaced acetabular fractures. If reduction was successful, the fractures were stabilized with percutaneous screws. Group 1 was composed of elderly patients with complex fractures and radiographic findings that were felt to be predictive of post-traumatic arthritis. In these patients, percutaneous screw fixation was used to improve fracture anatomy, allow mobilization and total hip replacement later, if necessary. In group 1, anatomical reduction was not felt to be a necessity. Group 2 was composed of young patients with simple fracture types. For group 2, anatomical reduction was the goal. In 23/24 patients, closed or limited open reduction was successful. In group 1, maximum displacement averaged 10 mm preoperatively, 3 mm postoperatively. In group 2, maximum displacement averaged 7 mm preoperatively, 1 mm postoperatively. One elderly patient was lost to follow-up and one died, leaving 21 patients with an average follow-up of 12 months. All the fractures healed. One patient had a transient femoral nerve palsy, and two elderly patients had minor losses of reduction due to unprotected ambulation after surgery. Five of the elderly patients have gone on to total hip arthroplasty. The average Harris Hip scores in groups 1 and 2 were 85 and 96, respectively.

Acetabulum↗

Visualization of secreted Hrp and Avr proteins along the Hrp pilus during type III secretion in Erwinia amylovora and Pseudomonas syringae.

Pili are required for protein and/or DNA transfer from bacteria to recipient plant or bacterial cells, based on genetic evidence. However, it has never been shown directly that the effector proteins or DNA are localized along or inside the pili in situ. Failure to visualize an association of effector proteins/DNA with pili is the central issue in the debate regarding the exact function of pili in protein and DNA transfer. In this study, a newly developed in situ immunogold labelling procedure enabled visualization of the specific localization of type III effector proteins of Erwinia amylovora and Pseudomonas syringae pv. tomato along the Hrp pilus, but not along the flagellum or randomly in the intercellular space. In contrast, PelE, a pectate lyase secreted via the type II protein secretion system, was not associated with the Hrp pilus. These results provide direct evidence that type III secretion occurs only at the site of Hrp pilus assembly and that the Hrp pilus guides the transfer of effector proteins outside the bacterial cell, favouring the 'conduit/guiding filament' model.

Animals↗

Isolation and characterization of five Erwinia amylovora bacteriophages and assessment of phage resistance in strains of Erwinia amylovora.

Phages able to infect the fire blight pathogen Erwinia amylovora were isolated from apple, pear, and raspberry tissues and from soil samples collected at sites displaying fire blight symptoms. Among a collection of 50 phage isolates, 5 distinct phages, including relatives of the previously described phages phiEa1 and phiEa7 and 3 novel phages named phiEa100, phiEa125, and phiEa116C, were identified based on differences in genome size and restriction fragment pattern. phiEa1, the phage distributed most widely, had an approximately 46-kb genome which exhibited some restriction site variability between isolates. Phages phiEa100, phiEa7, and phiEa125 each had genomes of approximately 35 kb and could be distinguished by their EcoRI restriction fragment patterns. phiEa116C contained an approximately 75-kb genome. phiEa1, phiEa7, phiEa100, phiEa125, and phiEa116C were able to infect 39, 36, 16, 20, and 40, respectively, of 40 E. amylovora strains isolated from apple orchards in Michigan and 8, 12, 10, 10, and 12, respectively, of 12 E. amylovora strains isolated from raspberry fields (Rubus spp.) in Michigan. Only 22 of 52 strains were sensitive to all five phages, and 23 strains exhibited resistance to more than one phage. phiEa116C was more effective than the other phages at lysing E. amylovora strain Ea110 in liquid culture, reducing the final titer of Ea110 by >95% when added at a ratio of 1 PFU per 10 CFU and by 58 to 90% at 1 PFU per 10(5) CFU.

Bacteriolysis↗

The Humphrey optical coherence tomography scanner: quantitative analysis and reproducibility study of the normal human retinal nerve fibre layer.

BACKGROUND/AIMS: To determine the reproducibility of the Humphrey optical coherence tomography scanner (OCT), software version 5.0, for measurement of retinal nerve fibre layer (RNFL) thickness in normal subjects and to compare OCT measurements with published histological thickness of the human RNFL. METHODS: Three independent measurements were obtained at each session for one eye from 15 normal subjects with a mean age of 30.8 (SD 10.9) years. Scans were taken in the peripapillary retina using the default setting (1.74 mm radius from centre of the optic disc) and were repeated 1 week later. Additional scans were obtained at the optic nerve head (ONH) margin overlying the scleral rim, for comparison with available histological data on the human RNFL. RESULTS: For the 1.74 mm circular scan, the mean coefficient of variation (COV) for the global RNFL thickness measurement was 5% (SD 3%). This increased to 8% (3%) for quadrant measurements and to 9% (3%) with further subdivision into 12 segments. Significant differences (p<0.05) between sessions were only found when the data were divided into segments. The mean RNFL thickness for the 1.74 mm scan was 127.87 (9.81) microm. The RNFL was maximal at the superior disc pole, 161.44 microm (14.8), and minimal at the temporal pole, 83.1 (12.8) microm. Peak thickness values occurred superior temporal and inferior temporal to the vertical axis. RNFL thickness for every sector of the disc was greatest at the margin of the optic disc (mean 185.79 microm; SD 32.61). Although the variation in RNFL thickness around the disc follows published histology data, the OCT underestimates RNFL thickness by an average of 37% (SD 11; range 21-48%). CONCLUSION: The OCT provides reproducible measurement of the retinal structures that are consistent with the properties of the RNFL. However, comparison with available studies of RNFL thickness in the human suggests that in its present form, the OCT underestimates RNFL thickness. Further refinement of this technology is required to improve the accuracy with which the OCT measures retinal nerve fibre layer thickness.

Adult↗

Measuring plasma paracetamol concentrations in all patients with drug overdose or altered consciousness: does it change outcome?

OBJECTIVE: To assess whether measuring plasma paracetamol concentrations in all patients with drug overdose or collapse (altered consciousness) changes outcome. METHOD: A retrospective survey was performed of all patients attending the Accident and Emergency Department at Guy's Hospital, London over a 12 month period who had plasma paracetamol concentrations measured (it is hospital policy that patients presenting after any drug overdose, or with a collapse/altered consciousness have a plasma paracetamol concentration). RESULTS: A total of 440 patients were identified who had plasma paracetamol concentrations measured, of whom 411 were eligible for the study. Altogether 115 patients presented after a collapse and paracetamol was detected in four of these. A total of 296 patients presented after a drug overdose-136 denied overdose with a paracetamol containing product and paracetamol was not detected in any of these 136 cases. Of the remaining 160 patients who gave a positive history for overdose with paracetamol, 122 presented within 24 hours and 94 had detectable paracetamol values with 16 cases above the treatment line, 12 presented more than 24 hours after ingestion, and 26 presented with a staggered overdose. One patient died as a result of paracetamol overdose. CONCLUSIONS: This is the first study in the United Kingdom to evaluate the clinical value of routine paracetamol levels in patients presenting to the emergency department after any overdose or a collapse. Taking blood samples for plasma paracetamol estimation in patients who deny taking paracetamol is of little clinical value. However, there is the potential for missing significant paracetamol poisoning in patients presenting with collapse and so screening with a plasma paracetamol concentration is clinically justified in these patients. Such an approach can only be justified in a country in which paracetamol poisoning is prevalent, such as the United Kingdom.

Acetaminophen↗

A prospective evaluation of the clinical utility of the lower-extremity injury-severity scores.

BACKGROUND: High-energy trauma to the lower extremity presents challenges with regard to reconstruction and rehabilitation. Failed efforts at limb salvage are associated with increased patient mortality and high hospital costs. Lower-extremity injury-severity scoring systems were developed to assist the surgical team with the initial decision to amputate or salvage a limb. The purpose of the present study was to prospectively evaluate the clinical utility of five lower-extremity injury-severity scoring systems. METHODS: Five hundred and fifty-six high-energy lower-extremity injuries were prospectively evaluated with use of five injury-severity scoring systems for lower-extremity trauma designed to assist in the decision-making process for the care of patients with such injuries. Four hundred and seven limbs remained in the salvage pathway six months after the injury. The sensitivity, specificity, and area under the receiver operating characteristic curve were calculated for the Mangled Extremity Severity Score (MESS); the Limb Salvage Index (LSI); the Predictive Salvage Index (PSI); the Nerve Injury, Ischemia, Soft-Tissue Injury, Skeletal Injury, Shock, and Age of Patient Score (NISSSA); and the Hannover Fracture Scale-97 (HFS-97) for ischemic and nonischemic limbs. The scores were analyzed in two ways: including and excluding limbs that required immediate amputation. RESULTS: The analysis did not validate the clinical utility of any of the lower-extremity injury-severity scores. The high specificity of the scores in all of the patient subgroups did confirm that low scores could be used to predict limb-salvage potential. The converse, however, was not true. The low sensitivity of the indices failed to support the validity of the scores as predictors of amputation. CONCLUSIONS: Lower-extremity injury-severity scores at or above the amputation threshold should be cautiously used by a surgeon who must decide the fate of a lower extremity with a high-energy injury.

Adolescent↗

Patient mood and carer strain during stroke rehabilitation in the community following early hospital discharge.

PURPOSE: Patient mood and carer stress were assessed for stroke patients in the community following early hospital discharge. METHOD: Patients had low Barthel Indices (13.0 (mean) +/- 4.9 (SD)) with high anxiety and depression scores, and carers had high stress scores, on starting rehabilitation. On starting rehabilitation, patient Barthel Indices correlated inversely with patient depression (r = -0.33, p < 0.02) and carer stress scores (r = -0.48, p < 0.001). RESULTS: During rehabilitation improvements occurred in patient Barthel Indices, patient anxiety scores and carer stress scores, but not in patient depression scores. Incremental increases in patient Barthel Indices during rehabilitation correlated with reductions in carer stress scores (r = -0.55, R2 = 29.4%, p < 0.001). Following early hospital discharge stroke patients display mood abnormalities which do not resolve during rehabilitation. CONCLUSION: Carer stress and patients depression scores are related to the severity of stroke-related disability. Strategies to address patient mood and carer stress should be present in community services providing early stroke rehabilitation.

Affect↗

Novel inhibitors of the condensing enzymes of the type II fatty acid synthase of pea (Pisum sativum).

The type II fatty acid synthases (FASs) of higher plants (and Escherichia coli) contain three condensing enzymes called beta-ketoacyl-ACP synthases (KAS), where ACP is acyl-carrier-protein. We have used novel derivatives of the antibiotic thiolactomycin to inhibit these enzymes. Overall de novo fatty acid biosynthesis was measured using [1-(14)C]acetate substrate and chloroplast preparations from pea leaves, and [1-(14)C]laurate was used to distinguish between the effects of the inhibitors on KAS I from those on KAS II. In addition, the activities of these enzymes, together with the short-chain condensing enzyme, KAS III, were measured directly. Six analogues were tested and two, both with extended hydrocarbon side chains, were found to be more effective inhibitors than thiolactomycin. Incubations with chloroplasts and direct assay of the individual condensing enzymes showed that all three compounds inhibited the pea FAS condensing enzymes in the order KAS II > KAS I > KAS III. These results demonstrate the general activity of thiolactomycin and its derivatives against these FAS condensation reactions, and suggest that such compounds will be useful for further detailed studies of inhibition and for use as pharmaceuticals against Type II FASs of pathogens.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

SAC3 may link nuclear protein export to cell cycle progression.

Selective movement of proteins between the nucleus and the cytoplasm is a regulatory mechanism exploited extensively by the eukaryotic cell. We have identified the evolutionarily conserved Sac3 protein, which was implicated previously in the regulation of mitosis [Bauer, A. & Kölling, R. (1996) J. Cell Sci. 109, 1575-1583] as a novel mediator of nuclear protein export. We show that Sac3p is localized to the nuclear pore, where it interacts with nucleoporins. Loss of SAC3 function results in a block in nuclear export of a nuclear export signal-containing reporter protein. Our results also demonstrate that SAC3 interacts genetically with the nuclear protein export factors Crm1p/Xpo1p and Yrb2p. Taken together, these data indicate a link between nuclear protein export and transition through the cell cycle.

Amino Acid Sequence↗

Sulfotransferases: genetics and role in toxicology.

The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzymes, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encoded by separate genes. Common functional polymorphisms of the transcribed region are known for two of the forms. We have expressed 16 separate rat and human SULTs as well as some of their allelic variants, in Salmonella typhimurium TA1538 and/or V79 cells, which are target cells of commonly used mutagenicity assays. The expressed SULTs activated numerous compounds to mutagens in both assay systems. However, some promutagens were activated by only one or several of the human SULTs. Pronounced differences in promutagen activation were also detected between orthologous rat and human SULTs, and between allelic variants of human SULTs.

Animals↗

Craniometric variation in a population of mantled howler monkeys (Alouatta palliata): evidence of size selection in females and growth in dentally mature males.

A large body of work on monkey cranial metrics (involving conclusions about interspecific variation, sexual dimorphism, and ontogeny) depends on the assumptions that growth effectively ceases with dental maturity and that intraspecific variation is negligible. We test these assumptions by examining variation in 39 measurements of 166 dentally mature Alouatta palliata skulls from animals found dead on Barro Colorado Island (BCI), Panama. We also investigate whether this population is under size-based selection, since our found-dead sample reflects the natural mortality in this population. The sample was divided into three age stages by occlusal wear (A-C, least to most wear). Female stage A means are significantly smaller than female stage B means for three cranial measures. Female stage B means are significantly smaller than female stage C means for five cranial measures. Male stage A means are significantly smaller than male stage B means for 21 cranial measures. Multivariate analyses confirm this trend of expansion between adult age stages. The dental metric and suture closure data suggest that the cranial expansion in females is due to size-based selection, while the cranial expansion in males is due to significant growth after dental maturity. Sexual dimorphism ratios are highly variable across different samples of A. palliata, indicating that dimorphism varies between populations of this species. These results provide insight into the selective forces operating on the BCI howlers and challenge the validity of the many studies which pool subspecies and assume growth ceases with maturity.

Aging↗

Reduction of azinphos-methyl, chlorpyrifos, esfenvalerate, and methomyl residues in processed apples.

McIntosh, Red Delicious, and Golden Delicious from two years of experimental spray programs using azinphos-methyl, chlorpyrifos, esfenvalerate, and methomyl were processed into frozen apple slices, applesauce, single-strength juice, and juice concentrate. Residue levels were expressed as micrograms per 150 g of apple or the equivalent amount of apple product to calculate the percentage change in these pesticides brought about by processing. Producing single-strength apple juice reduced azinphos-methyl, chlorpyrifos, esfenvalerate, and methomyl residues by 97.6, 100, 97.8, and 78.1%, respectively. Production of applesauce reduced all four compounds by >/=95%. Azinphos-methyl, chlorpyrifos, esfenvalerate, and methomyl residues were reduced in apple slices by 94.1, 85.7, 98.6, and 94.7%, respectively. Processing is shown to be very effective in reducing the levels of these pesticides.

Azinphosmethyl↗

Identification of Streptococcus agalactiae virulence genes in the neonatal rat sepsis model using signature-tagged mutagenesis.

Group B streptococcal (GBS) infections are the most common cause of bacterial sepsis in the immediate newborn period. Apart from the capsule, the factors required for survival of GBS in the host are not well defined. In this study, signature-tagged transposon mutagenesis (STM) was used to identify genes required for growth and survival of GBS in a neonatal rat sepsis infection model. Approximately 1600 transposon mutants were screened in pools of 80 mutants, and approximately 120 mutants defective for survival in the animal host were identified. We successfully cloned and sequenced DNA flanking the transposon insertions from 92 of the mutants. Fifty per cent of the mutants had transposon insertions in genes with homologues in the public databases, whereas the remaining 50% had transposon insertions in genes with unknown function. A significant proportion of the avirulent mutants had transposon insertions in genes encoding transport-associated or regulatory proteins or in genes involved in cell surface metabolism, emphasizing the significance of these functions for in vivo survival of GBS. Overall, STM analysis revealed GBS genomic loci that encode a wide variety of functional gene classes, underscoring the diversity of bacterial processes required for the infection process. Currently, the function of the genes identified during the screening can only be inferred by homology to previously described genes. However, a number of the genes identified in this study have been shown to correlate with virulence in other pathogens. A virulence of a subset of mutants identified during the screening was confirmed by performing competitive index assays and lethal dose assays. This represents the first report of a genome-wide scan for virulence factors in GBS. The identified genes will further our understanding of the pathogenesis of GBS infections and may represent targets for intervention or lead to the development of novel therapies.

Animals↗

Toxicity of high-activity 111In-Octreotide therapy in patients with disseminated neuroendocrine tumours.

Disseminated neuroendocrine tumours are difficult to treat and are generally not responsive to radiotherapy or chemotherapy. Nuclear medicine techniques using a radiolabelled somatostatin analogue, 111In-Octreotide, have been used for the diagnosis of neuroendocrine tumours. It has been suggested that high activities of such an agent may have a therapeutic effect. The aims of this study were to assess toxicity and to determine if there had been evidence of efficacy. Eight patients with known disseminated neuroendocrine tumours were enrolled in the study; six had carcinoid tumours, one had a medullary cell carcinoma of the thyroid and one patient had a malignant gastrinoma. Between 1.3 and 4.6 GBq of 111In-Octreotide were administered to each patient for up to five administrations over 12 months. A total of 23 administrations were given. Tests of vital signs, renal, liver and endocrine function as well as haematological markers were taken before and after treatment. The treatment was well tolerated with only one patient suffering from a sensation of flushing during the infusion but no changes in vital sings. There was a transient (up to 48 h) drop in circulating lymphocytes in four patients and platelets in two patients; no supportive therapy was needed. One patient with severe renal impairment had a slight reduction in glomerular filtration rate. We conclude that high-activity 111In-Octreotide is well tolerated with low toxicity and can be considered for use in patients with disseminated neuroendocrine tumours. Further work is now being performed to assess efficacy.

Adult↗

Complete nucleotide sequence of ubiquitous plasmid pEA29 from Erwinia amylovora strain Ea88: gene organization and intraspecies variation.

The complete sequence of plasmid pEA29 from Erwinia amylovora strain Ea88 consists of 28,185 bp with a 50.2% G+C content. As deletions and insertions were detected in other derivatives of pEA29, its size actually varied from 27.6 to 34.9 kb. Thirteen open reading frames that encoded predicted proteins with similarities to known proteins from other bacteria were identified along with two open reading frames related to hypothetical proteins found in GenBank and six open reading frames with no similarities to existing GenBank entries. Predicted products of open reading frames with similarity to the thiamine biosynthetic genes thiO, thiG, and thiF; a betT gene coding for choline transport; an msrA gene for the enzyme methionine sulfoxide reductase; a putative methyl-accepting chemotaxis gene; an aldehyde dehydrogenase gene; an hns DNA binding gene; a LysR-type transcriptional regulator; and parA and parB partitioning genes were identified. A putative iteron-containing theta-type origin of replication with an AT-rich region and a gene for a RepA protein was identified. PstI and KpnI restriction patterns for pEA29 isolated from tree fruit strains of E. amylovora were homogenous and different from those for pEA29 isolated from Rubus (raspberry) strains. All Rubus derivatives of pEA29 contained a point mutation that eliminated a PstI site and a 1,264-bp region that replaced 1, 890 bp of sequence found in pEA29 from strain Ea88. This change eliminated a second PstI site and increased the length of a KpnI fragment. An insertion sequence, ISEam1, was detected in one Rubus strain, and transposon Tn5393 was detected in three apple strains in two separate locations on the plasmid. Plasmid-cured strains exhibited reduced virulence and modified colony morphology on minimal medium without thiamine, indicating that some of the genes in pEA29 play a role in the physiology or metabolism of E. amylovora.

Base Sequence↗

A case of lead poisoning due to snooker chalk.

A 3 year, 9 month old child with pica presented with a blood lead concentration of 1.74 micromol/l (360 microg/l). The source of poisoning was snooker chalk (lead content 7200 microg/g). She was treated with intravenous calcium disodium edetate chelation. Thirty months later her blood lead was 0.39 micromol/l (80 microg/l). This case illustrates the need to be vigilant for more unusual causes of lead poisoning in the home.

Calcium Carbonate↗