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Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

224 records · Page 13Linked to original sources

Hepatic responses to the administration of high doses of BHT to the rat: their relevance to hepatocarcinogenicity.

Although butylated hydroxytoluene (BHT) is non-mutagenic, at high doses it has recently been associated with an increased incidence of liver tumours in laboratory rodents. To establish whether chronic liver cell injury may be involved in the genesis of these tumours, BHT was administered to rats by orogastric gavage at doses of 0, 25, 250 or 500 mg/kg/day for up to 28 days and also at daily doses of 1000 and 1250 mg BHT/kg for up to 4 days (sublethal doses). The sublethal doses induced centrilobular necrosis within 48 hr, whereas administration of BHT for 7 or 28 days caused dose-related hepatomegaly and at the highest dose level induced progressive periportal hepatocyte necrosis. The periportal lesions were associated with proliferation of bile ducts, persistent fibrous and inflammatory cell reactions, hepatocyte hyperplasia and hepatocellular and nuclear hypertrophy. Biochemical changes consisted of dose-related induction of epoxide hydrolase, dose-related changes in the ratio of cytochrome P-450 isoenzymes and depression of glucose-6-phosphatase. Measurement of BHT demonstrated a dose-related accumulation in fat but not in the liver. Changes in hepatic activating and detoxifying enzyme profiles are implicated both in the mechanism of periportal hepatocyte damage and in the change of site of damage according to the dose and duration of the treatment. The persistent and active nature of the lesions in rats dosed with 500 mg BHT/kg for 28 days, combined with evidence of cell damage at doses equivalent to those associated with hepatic tumours (250 mg BHT/kg), suggests that chronic liver cell damage may be involved in their aetiology. In this and several other studies, there was no evidence that BHT causes liver damage at a dose level of 25 mg/kg/day. As this is several hundred times higher than the normal human intake, it is considered unlikely that BHT poses a threat to human health.

Adipose Tissue↗

Quantification of the putative neurotoxin 2-amino-3-(methylamino)propanoic acid (BMAA) in cycadales: analysis of the seeds of some members of the family Cycadaceae.

Over the past 30 years there have been attempts to link the unusually high incidence of amyotrophic lateral sclerosis (ALS) among the Chamorros native to the island of Guam to the consumption of the seeds of Cycas circinalis L., the false sago palm. In support of this relationship it was recently shown that, when given to primates, 2-amino-3-(methylamino)-propanoic acid (BMAA), a minor cycad component, can cause selective degeneration of upper and lower motor neurons in the spinal cord and clinical features similar to those of ALS. In order to test the relationship between ALS and cycads, we have developed a sensitive and precise gas chromatographic/mass spectrometric (GC/MS) assay for BMAA which allows direct assessment of the BMAA content in foods and is directly applicable to the assay of BMAA in biologic tissues and fluids. After the addition of a deuterated isotopomer as an internal standard and transesterication with 2-methyl-1-propanol, BMAA was extracted into dichloromethane and then acylated with pentafluoropropionic anhydride before GC/MS. This method permits precise quantification of BMAA in the low picogram/sample range. Direct quantification of the BMAA content in the female gametophyte tissue (endosperm) of a range of cycad seeds collected from Guam confirmed the presence of BMAA at levels of approximately 1 g/g (dry weight). The presence of BMAA in the seed extract was confirmed after derivatization of an aliquot of the extract and GC/MS analysis in the scanning mode. BMAA was found to be present, albeit at lower levels, in the endosperm of the seeds of C. revoluta (0.32 mg/g) and C. media (0.29 mg/g).

Amino Acids, Diamino↗

Investigation of an FFT-based correlation technique for verification of radiation treatment setup.

Electronic portal imaging devices that capture an image of a patient's treatment field electronically by means of a computer data acquisition system operating in real time are becoming available. This paper reports on a study of a field verification correlation algorithm that can compare each treatment portal image to an image of the correct treatment field positioning. The algorithm requires no human intervention or analysis of the images but rather uses fast Fourier transforms to produce a correlation distribution. The position and amplitude of the correlation distribution maximum were tested as objective measures of translational and rotational differences of subject positions between pairs of images. The concept was tested by using a prototype algorithm to obtain the correlation distributions for images of an Alderson Rando head phantom. Images of the phantom setup with various errors were compared with an image of the phantom in the initial, correct treatment position. Translations, in-plane and out-of-plane rotations, and combinations of translations and rotations were studied. The algorithm accurately measured translations. The value of the correlation distribution maximum was found to be a reasonable candidate for an alignment parameter for which tolerable error thresholds might be established.

Algorithms↗

Osteoporosis in rheumatoid arthritis.

Osteoporosis is recognised as a common complication of rheumatoid arthritis, with two characteristic patterns--juxta-articular and generalized bone loss. Increasingly sophisticated means of measuring bone turnover and identifying inflammatory mediators which affect bone resorption have enhanced our understanding of the disease process. The aetiology is multifactorial, involving disease-specific and general factors, but the relative importance of the various risks remains uncertain. The evidence for a protective role for oestrogens and the detrimental effect of low dose corticosteroids will be discussed. Biochemical assessment of bone loss lacks sensitivity and specificity, but the rapid improvement in radiological techniques for measuring bone mineral density have improved our ability to diagnose and assess disease progression. The diagnosis and treatment of specific risk factors, such as testosterone or vitamin D deficiency, may be helpful in a few patients, but the ultimate aim must be the early diagnosis and prevention of this potentially catastrophic complication.

Adrenal Cortex Hormones↗

Coexisting polyostotic fibrous dysplasia and Paget's disease.

The following case report describes a patient who is known to have both fibrous dysplasia and Paget's disease, and traces his history over more than 50 years. The similarities and differences between the two conditions and their relative importance at the various stages of the history are discussed.

Aged↗

The Evaluation of the Resolving Conflict Creatively Program: an overview.

The Resolving Conflict Creatively Program (RCCP) is a comprehensive, school-based program in conflict resolution and intercultural understanding implemented in more than 110 New York City public schools. The National Center for Children in Poverty is currently conducting an evaluation of the program in grades 1-6, although the program itself is implemented in grades K-12. The following components are included: teacher training, classroom instruction and staff development, the program curriculum, administrators' training, peer mediation, parent training, and a targeted intervention for high-risk youth. The program evolved out of practice-based theory. Researchers and practitioners have collaborated on and designed an evaluation that illustrates how the practice-based theory is consistent with and can be put into operation using developmental and ecological theories of the etiology of violence-related behaviors in middle childhood. The target population for this study is approximately 9,600 children, 5-12 years of age, in 15 elementary schools in New York City. The evaluation is being conducted over two years with two data-collection points in each year. A cross-sequential design is being used to examine the short- and intermediate-term utility with children at different ages/developmental stages. The relative effect of the beginning program can be compared to more comprehensive models. A total of 8,233 students responded to the baseline survey. The study population is largely Hispanic (41%) and African American (37%). Preliminary analyses indicate that baseline means of such constructs as aggressive fantasies, hostile attributional biases, and conduct problems increase with grade level. Ten years of practice-based experience and one year of a two-year quantitative evaluation have taught several important lessons about school-based program implementation and the evaluation of such programs. The scope and longevity of the RCCP and the empirically rigorous evaluation now under way will make a significant contribution to the field of violence prevention and field-based program evaluation.

Age Distribution↗

Short latency vestibular evoked potentials in the chicken embryo.

Electrophysiological responses to pulsed linear acceleration stimuli were recorded in chicken embryos incubated for 19 or 20 days (E19/E20). Responses occurred within the first 16 ms following the stimulus onset. The evoked potentials disappeared following bilateral labyrinthectomy, but persisted following cochlear destruction alone, thus demonstrating that the responses were vestibular. Approximately 8 to 10 response peaks could be identified. The first 4 positive and corresponding negative components (early peaks with latencies < 6.0 ms) were scored and latencies and amplitudes quantified. Vestibular response latencies were significantly longer (P < 0.01) and amplitudes significantly smaller (P < 0.001) than those observed in 2-week-old birds. Mean response threshold for anesthetized embryos was -15.9dBre 1.0 g/ms, which was significantly higher (P < 0.03) than those observed in 2-week-old birds (-23.0dBre 1.0 g/ms). Latency/intensity functions (that is, slopes) were not significantly different between embryos and 2-week-old animals, but amplitude/intensity functions for embryos were significantly shallower than those for 2-week-old birds (P < 0.001). We presume that these differences reflect the refinement of sensory function that occurs following 19 to 20 days of incubation. The recording of vestibular evoked potentials provides an objective, direct and noninvasive measure of peripheral vestibular function in the embryo and, as such, the method shows promise as an investigative tool. The results of the present study form the definitive basis for using vestibular evoked potentials in the detailed study of avian vestibular ontogeny and factors that may influence it.

Acceleration↗

The adequate stimulus for avian short latency vestibular responses to linear translation.

Transient linear acceleration stimuli have been shown to elicit eighth nerve vestibular compound action potentials in birds and mammals. The present study was undertaken to better define the nature of the adequate stimulus for neurons generating the response in the chicken (Gallus domesticus). In particular, the study evaluated the question of whether the neurons studied are most sensitive to the maximum level of linear acceleration achieved or to the rate of change in acceleration (da/dt, or jerk). To do this, vestibular response thresholds were measured as a function of stimulus onset slope. Traditional computer signal averaging was used to record responses to pulsed linear acceleration stimuli. Stimulus onset slope was systematically varied. Acceleration thresholds decreased with increasing stimulus onset slope (decreasing stimulus rise time). When stimuli were expressed in units of jerk (g/ms), thresholds were virtually constant for all stimulus rise times. Moreover, stimuli having identical jerk magnitudes but widely varying peak acceleration levels produced virtually identical responses. Vestibular response thresholds, latencies and amplitudes appear to be determined strictly by stimulus jerk magnitudes. Stimulus attributes such as peak acceleration or rise time alone do not provide sufficient information to predict response parameter quantities. Indeed, the major response parameters were shown to be virtually independent of peak acceleration levels or rise time when these stimulus features were isolated and considered separately. It is concluded that the neurons generating short latency vestibular evoked potentials do so as "jerk encoders" in the chicken. Primary afferents classified as "irregular", and which traditionally fall into the broad category of "dynamic" or "phasic" neurons, would seem to be the most likely candidates for the neural generators of short latency vestibular compound action potentials.

Acceleration↗