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Biomedical subjects

J R Walton

Publications and source records attributed to J R Walton.

At least 19 recordsLinked to original sources

A longitudinal study of rats chronically exposed to aluminum at human dietary levels.

According to the World Health Organization, oral ingestion of aluminum additives is the main form of aluminum exposure for the general public. Aluminum salts are added to a range of commercially-prepared foods and beverages: to clarify drinking water, make salt free-pouring, color snack/dessert foods, and make baked goods rise. In the present study, six Wistar rats chronically consumed aluminum from 16 months of age to the conclusion of their lifespan (averaging 29.8 months) in an amount (1.5mg/kg bodyweight) equivalent to the high end of the total aluminum range ingested daily by humans living in contemporary urban society. The rats were memory-trained in a continuous rewarded alternation T-maze task and tested weekly from 5 months of age onwards. This longitudinal study compared their mean memory performances over 15 consecutive weeks during middle age (12-23 months) and old age (> or =24 months). Four out of six rats continued to perform the memory task in old age without significant deficit. The remaining two obtained significantly lower mean memory scores in old age than in middle age and exhibited soft signs associated with dementia. Their hippocampal neurons stained for aluminum, showing some but not all features of aluminum accumulation that occur in human hippocampal neurons. In view of evidenced linkages of aluminum with beta-amyloid plaque and neurofibrillary tangle formation in humans with Alzheimer's disease, the findings suggest this protocol is worth testing in larger groups of animals.

Administration, Oral↗

Aluminum in hippocampal neurons from humans with Alzheimer's disease.

Using a staining technique developed in 2004, we examined hippocampal tissue from autopsy-confirmed cases of Alzheimer's disease (AD) and controls. The stain disclosed aluminum in cells and subcellular structure. All pyramidal neurons in these aged specimens appeared to exhibit at least some degree of aluminum staining. Many displayed visible aluminum only in their nucleolus. At the other extreme were neurons that stained for aluminum throughout their nucleus and cytoplasm. The remainder exhibited intermediate degrees of staining. On the basis of their aluminum staining patterns, all pyramidal neurons could be classified into stages that indicated two distinct neuropathological processes, either (1) progressive increase of nuclear aluminum (often accompanied by granulovacuolar degeneration with granules that stain for aluminum) or (2) formation of neurofibrillary tangles (NFTs) in regions of aluminum-rich cytoplasm, especially in AD brain tissue. In the latter process, intraneuronal NFTs appeared to displace nuclei and then enucleate the affected neurons during the course of their transformation into extracellular NFTs. Given that the NFTs we observed in human neurons always developed in conjunction with cytoplasmic aluminum, we hypothesize that aluminum plays an important role in their formation and should therefore be reconsidered as a causative factor for AD.

Aged↗

Improved morphed potentials for Ar-HBr including scaling to the experimentally determined dissociation energy.

A lead salt diode infrared laser spectrometer has been employed to investigate the rotational predissociation in Ar-HBr for transitions up to J' = 79 in the v(1) HBr stretching vibration of the complex using a slit jet and static gas phase. Line-shape analysis and modeling of the predissociation lifetimes have been used to determine a ground-state dissociation energy D(0) of 130(1) cm(-1). In addition, potential energy surfaces based on ab initio calculations are scaled, shifted, and dilated to generate three-dimensional morphed potentials for Ar-HBr that reproduce the measured value of D(0) and that have predictive capabilities for spectroscopic data with nearly experimental uncertainty. Such calculations also provide a basis for making a comprehensive comparison of the different morphed potentials generated using the methodologies applied.

Journal Article↗

A mathematical model of atherogenesis as an inflammatory response.

We construct a mathematical model of the early formation of an atherosclerotic lesion based on a simplification of Russell Ross' paradigm of atherosclerosis as a chronic inflammatory response. Atherosclerosis is a disease characterized by the accumulation of lipid-laden cells in the arterial wall. This disease results in lesions within the artery that may grow into the lumen restricting blood flow and, in critical cases, can rupture causing complete, sudden occlusion of the artery resulting in heart attack, stroke and possibly death. It is now understood that when chemically modified low-density lipoproteins (LDL cholesterol) enter into the wall of the human artery, they can trigger an immune response mediated by biochemical signals sent and received by immune and other cells indigenous to the vasculature. The presence of modified LDL can also corrupt the normal immune function triggering further immune response and ultimately chronic inflammation. In the construction of our mathematical model, we focus on the inflammatory component of the pathogenesis of cardiovascular disease (CVD). Because this study centres on the interplay between chemical and cellular species in the human artery and bloodstream, we employ a model of chemotaxis first given by E. F. Keller and Lee Segel in 1970 and present our model as a coupled system of non-linear reaction diffusion equations describing the state of the various species involved in the disease process. We perform numerical simulations demonstrating that our model captures certain observed features of CVD such as the localization of immune cells, the build-up of lipids and debris and the isolation of a lesion by smooth muscle cells.

Atherosclerosis↗

A new paradigm for graduate research and training in the biomedical sciences and engineering.

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.

Biological Science Disciplines↗

Diagnosis of rotator cuff tears.

Rotator cuff tears account for almost 50% of major shoulder injuries but are sometimes difficult to diagnose. To aid diagnosis, we did a prospective study, comparing results of 23 clinical tests from 400 patients with and without rotator cuff tears. Three simple tests were predictive for rotator cuff tear: supraspinatus weakness, weakness in external rotation, and impingement. When all three were positive, or if two tests were positive and the patient was aged 60 or older, the individual had a 98% chance of having a rotator cuff tear; combined absence of these features excluded this diagnosis.

Adult↗

Reliability of five methods for assessing shoulder range of motion.

In symptomatic subjects, the reliability of tests for shoulder joint range of motion has yet to be determined. For this reason, inter-rater and intra-rater agreement trials were undertaken to ascertain the reliability of visual estimation, goniometry, still photography, "stand and reach" and hand behind back reach for six different shoulder movements. Intra-class correlation coefficients (Rho) were derived by using a random effects model. For flexion, abduction and external rotation fair to good reliability was demonstrated for both trials using visual estimation (Inter-rater Rho = 0.57-0.70; Intra-rater Rho = 0.59-0.67), goniometry (Inter-rater Rho = 0.64-0.69; Intra-rater Rho = 0.53-0.65) and still photography (Inter-rater Rho = 0.62-0.73; Intra-rater Rho = 0.56-0.61). The tests had standard errors of measurement of between 14 and 25 degrees (inter-rater trial) and 11 and 23 degrees (intra-rater trial).

Adult↗

The impact of war on the mental health of children: a Salvadoran study.

OBJECTIVE: This ecologically conceptualized, intensive study assesses the mental health impact of the Salvadoran Civil War on 54 12-year-olds, born into the war, exposed to different levels of war violence. METHODS: Half of the students came from a repopulated country village and half from an industrial neighborhood near the capital city. Children, their mothers or caretakers, and their teachers responded to interviews and some instruments. RESULTS: Children from the repopulated village reported higher war experience and lower mental health. The personal/social impact of the war was more important than family togetherness or war intensity in determining the mental health of the children. Children's intelligence was highly related to surviving with higher mental health. Higher socioeconomic status (SES) and education of parents was related to better mental health. Controlling for intelligence, children who experienced the highest personal-social impact of war showed the poorest mental health. Children with high war experience were most likely to have difficulty in imagining the future. CONCLUSIONS: Intelligence and the foreshortening of future vision are variables that should be controlled for and investigated in outcome studies of trauma. Treatment for survivors should include aid in planning for the future.

Adaptation, Psychological↗

Apramycin-resistant Escherichia coli isolated from pigs and a stockman.

Escherichia coli serotype O147:K89:K88a,c was found to be associated with outbreaks of diarrhoea in preweaner pigs of up to 4 weeks of age on a pig unit. Resistance to apramycin, gentamicin, netilmicin, tobramycin and other antibiotics was associated with conjugative plasmids of approximately 62 kb. The presence of a gene which encoded for the aminoglycoside acetyltransferase enzyme AAC(3)IV was confirmed by DNA hybridization. Samples collected during the following 12 months revealed widespread dissemination of these resistance plasmids in non-serotypable, non-haemolytic E. coli throughout the farm. Apramycin-resistant E. coli were also isolated from a stockman and it appeared from plasmid profile analysis and antibiotic sensitivity testing that the human isolates carried the same plasmid as that carried by the porcine E. coli. Klebsiella pneumoniae, with a slightly smaller conjugative plasmid and similar resistance pattern, was isolated from the stockman's wife.

Agricultural Workers' Diseases↗

Bacterial flora of the urinary tract of pigs associated with cystitis and pyelonephritis.

Twenty-three cases of porcine cystitis and pyelonephritis were examined bacteriologically. Eubacterium suis was found in 21 cases. The isolation of large numbers of Escherichia coli in the upper urinary tract was associated with linear renal scarring. An unidentifiable streptococcus and Enterococcus faecalis were isolated from a case of purulent ureteritis, pyelitis and pyelonephritis. The bacterial flora from cases of cystitis and pyelonephritis was different from that isolated from sows with asymptomatic bacteriuria.

Animals↗

Observations on anatomical aspects of the ureterovesical junction of the pig.

The paper reports the anatomy of the ureterovesical junction in pigs without urinary tract disease and the changes that occur with ageing. In comparison with other mammals the pig has a long intravesical ureter. Its length increases with age, from a mean length of 5 mm. at birth to 36 mm. at maturity. The width of the ureteric orifice also increases with age. The ureteric orifice was horseshoe shaped in 96.5% of cases, the remaining orifices were stadium shaped. The delineation of the anatomy of the porcine UVJ is important in the study of porcine and human pyelonephritis as the pig urinary tract is widely used as a human model.

Animals↗

Human isolates of apramycin-resistant Escherichia coli which contain the genes for the AAC(3)IV enzyme.

Gentamicin-resistant Escherichia coli isolated at different periods from patients in two hospitals were tested for resistance to the aminoglycoside antibiotic apramycin. Twenty-four of 93 (26%) gentamicin-resistant isolates collected from the Royal Liverpool Hospital between 1981 and 1990 were resistant to apramycin. Thirteen isolates were highly resistant to apramycin (minimal inhibitory concentration (MIC) > or = 1024 micrograms/ml), were also resistant to gentamicin, netilmicin and tobramycin, and hybridized with a DNA probe derived from the aminoglycoside acetyltransferase (3)IV (AAC(3)IV) gene. The proportion of gentamicin-resistant isolates which had high level resistance to apramycin increased from 7% in 1981-5 to 24% in 1986-90. Twelve gentamicin-resistant E. coli from Guy's and St Thomas's Hospital isolated between 1977 and 1980 were also tested for resistance to apramycin. For five of these isolates the MICs of apramycin was 32-256 micrograms/ml. None was shown to have a conjugative plasmid carrying resistance to apramycin and only one hybridized with the DNA probe for the AAC(3)IV enzyme.

Acetyltransferases↗

Reproductive wastage in the androstenedione-immune ewe.

An experiment was carried out using 320 adult Merino ewes to examine the effects of immunization against an androstenedione human serum albumin conjugate (Fecundin) on ovulation rate, fertilization rate and embryo viability at days 2, 9 and 13-14 after fertilization. The ovulation rate of immunized ewes (2.19 +/- 0.06) was greater (P < 0.001) than that of control ewes (1.43 +/- 0.04). The recovery rate of embryos or of unfertilized oocytes on day 2 was reduced in immunized ewes, but fertilization rate of recovered oocytes was unaffected by immunization. The mean number of normal embryos per ewe pregnant (prolificacy) was higher and the proportion of ewes pregnant (fertility) was lower in immunized than in the control ewes. The distribution of the number of cells per embryo showed no differences in developmental age over the period of sampling, the majority of embryos at this time being at the two- to four-cell stage of development. At day 9 of pregnancy, blastocyst recovery rates were lower in immunized than in control ewes. About 90% of blastocysts recovered were developing normally in control ewes compared with 64% in immunized ewes. The majority of blastocysts recovered on day 9 had hatched from the zona pellucida prior to recovery (mean values were 94.2% and 87.8% for control and immunized groups, respectively). In control ewes single blastocysts were larger than twin blastocysts, but for the immunized ewes this difference was not significant. Both single blastocysts (P < 0.01) and twin blastocysts (P < 0.05) from immunized ewes were smaller than those from control ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗

Reduction in the length of the intravesical ureter associated with pyelonephritis in the adult pig.

The ureterovesical junction of pigs with cystitis and pyelonephritis was examined. There was significant shortening of the intravesical portion of the ureter in sows with pyelonephritis. In cases associated with acute pyelonephritis the ureteric orifice was found to be significantly wider than that found in the normal population. The ratio of the intravesical length to the ureteric orifice diameter was also significantly reduced. It is postulated that these changes to the ureterovesical junction originate or are caused by the disease processes in the bladder and may allow vesicoureteric reflux to occur, leading to ascending pyelonephritis.

Animals↗

Apramycin resistance plasmids in Escherichia coli: possible transfer to Salmonella typhimurium in calves.

An outbreak of salmonellosis in calves was monitored for persistence of Salmonella typhimurium excretion in faeces and the effect of treatment with apramycin. Prior to treatment apramycin-resistant Escherichia coli were present but all S. typhimurium isolates were sensitive. Following the treatment of six calves with apramycin, apramycin-resistant S. typhimurium were isolated from two treated calves and one untreated calf. Plasmid profiles of E. coli and S. typhimurium were compared and plasmids conferring resistance to apramycin and several other antibiotics were transferred by conjugation in vitro from calf E. coli and S. typhimurium isolates to E. coli K-12 and from E. coli to S. typhimurium. The plasmids conjugated with high frequency in vitro from E. coli to S. typhimurium, and hybridized to a DNA probe specific for the gene encoding aminoglycoside acetyltransferase 3-IV (AAC(3)-IV) which confers resistance to apramycin, gentamicin, netilmicin and tobramycin.

Animals↗