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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 217 records · Page 12Linked to original sources
PubMed2000

Combined RAF1 protein expression and p53 mutational status provides a strong predictor of cellular radiosensitivity.

The tumour suppressor gene, p53, and genes coding for positive signal transduction factors can influence transit through cell-cycle checkpoints and modulate radiosensitivity. Here we examine the effects of RAF1 protein on the rate of exit from a G2/M block induced by gamma-irradiation in relation to intrinsic cellular radiosensitivity in human cell lines expressing wild-type p53 (wtp53) protein as compared to mutant p53 (mutp53) protein. Cell lines which expressed mutp53 protein were all relatively radioresistant and exhibited no relationship between RAF1 protein and cellular radiosensitivity. Cell lines expressing wtp53 protein, however, showed a strong relationship between RAF1 protein levels and the radiosensitivity parameter SF2. In addition, when post-irradiation perturbation of G2/M transit was compared using the parameter T50 (time after the peak of G2/M delay at which 50% of the cells had exited from a block induced by 2 Gy of irradiation), RAF1 was related to T50 in wtp53, but not mutp53, cell lines. Cell lines which expressed wtp53 protein and high levels of RAF1 had shorter T50s and were also more radiosensitive. These results suggest a cooperative role for wtp53 and RAF1 protein in determining cellular radiosensitivity in human cells, which involves control of the G2/M checkpoint.

Amino Acid Sequence↗
PubMed2000

The Ceylon malaria epidemic of 1934-35: a case study in colonial medicine.

In 1934-35 Ceylon suffered a major malaria epidemic which affected one and a half million people out of a population of five and a half million. This paper will first examine the orgins and course of the epidemic but the main focus is on the measures the authorities adopted to deal with the disaster. In 1931 Ceylon had attained 'home rule' under the Donoughmore Constitution. The epidemic was a first and major test of the efficacy of the new government. Examining the responses of the imperial government, the colonial government and the colonial medical services to this medical emergency establishes that the epidemic was a turning point in the health services of Ceylon and thus Sri Lanka, that the legacy of colonial medicine is essentially mixed and that the complexity and contradictory nature of colonial medicine can only be understood by detailed contextual research.

Colonialism↗
PubMed2000

Introducing ropivacaine into a department's epidural analgesic practice. Improving acute pain service practice.

The results of introducing a new licensed local anaesthetic drug, ropivacaine, into routine practice were evaluated by measuring the efficacy and adverse effects of patient controlled epidural analgesia (PCEA), using ropivacaine 2 mg/ml (R), or the mixtures in current use: fentanyl 5 (micrograms/ml with bupivacaine 1 mg/ml (BF5) and fentanyl 10 (micrograms/ml) with bupivacaine 1 mg/ml (BF10). All patients were nursed on general wards after surgery. For two months, 102 consecutive patients were studied. Pain scores at rest were significantly better in the fentanyl and bupivacaine groups, (mean rank R: 35.5, BF5: 22.7, BF10: 26.9, P < 0.05). There was a significant correlation between patient controlled boluses and pain at rest and (p < 0.001), and pain on moving (p < 0.001). Nausea and vomiting was worse in the BF10 (p < 0.05). Older patients demanded less analgesia (p < 0.001). Postoperatively BF5 provided better pain relief with trends demonstrating fewer side-effects and complications than BF10 or R. We now use fentanyl 5 (micrograms/ml and bupivacaine 1 mg/ml as our standard epidural infusion mixture.

Adjuvants, Anesthesia↗
PubMed2000

Gastrointestinal symptoms and subjects cluster into distinct upper and lower groupings in the community: a four nations study.

OBJECTIVE: It is unknown whether distinct functional GI (GI) symptom groupings occur in the general population and whether these are similar across different cultures. Although symptom-based diagnostic criteria have been developed for upper and lower GI syndromes (the Rome criteria), the classification is controversial. We aimed to identify whether independent symptom-based subgroups exist in four countries consistent with the Rome criteria. METHODS: Random samples of the community were mailed a validated questionnaire based on the Bowel Disease Questionnaire in Rochester, MN (n = 2,220), in Sydney, Australia (n = 1,135), and in Essen, Germany (n = 500). A different validated questionnaire was mailed to a random sample in Osthammar, Sweden (n = 1,517). Only the common questions (n = 22) were used in the current analysis, and these were essentially identical in wording. The underlying structure of the item responses was examined using factor analysis. Initial factors were extracted using principal components analysis and then rotated using Varimax. Clustering of symptoms among individuals was examined though cluster analysis, using the factors as the basis for clustering. RESULTS: Response rates varied from 64% to 80%; responders and nonresponders were similar sociodemographically. All four studies yielded similar factor structures. All countries reported symptom groupings consistent with the irritable bowel syndrome (IBS), dyspepsia and/or gastroesophageal reflux, and constipation; all except Sweden also had a diarrhea group. The cluster analysis yielded slightly more disparate results but a healthy group was present in all populations. All four populations had an IBS and/or bowel dysfunction cluster identified; a gastroesophageal reflux cluster was also present in all countries. CONCLUSIONS: The similarity of factor and cluster structures found in these four nations suggest that patterns of GI symptoms and groupings of individuals are similar across these Western cultures. These results are consistent with the current international Rome classification for separate upper and lower functional GI disorders.

Adult↗
PubMed2000

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV(1)) were recorded and histamine provocative concentration causing a 20% fall in FEV(1) (PC(20)) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.

Adult↗
PubMed2000

Forced expiratory flows and volumes in infants. Normative data and lung growth.

Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Anthropometry↗
PubMed2000

Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia.

Infection with the human immunodeficiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.

AIDS Dementia Complex↗
PubMed2000

Northern exposure.

The operators of Alaska's Alyeska pipeline have often claimed an outstanding record in preventing accidents and environmental damage. This article highlights that, contrary to these claims, Alyeska's operations have brought with them a life-threatening gamble with Alaska's fragile environment. The authors document how the operators of Alyeska have misled the public about the company's real safety record, while at the same time preventing employees from speaking out. As the oil companies consolidate globally, territorial entities such as Alaska can literally assume the character of an oil province.

Journal Article↗
PubMed2000

Detection of the human immunodeficiency virus regulatory protein tat in CNS tissues.

Neuropathologically, human immunodeficiency virus (HIV) is associated with a range of inflammatory disorders, extensive cortical neuronal loss, and dendritic and synaptic damage. Although the mechanisms resulting in these abnormalities are still unclear, the neurotoxic effects are thought to be due in part to viral products including the tat gene product. We have previously shown that Tat when presented to neurons extracellularly interacts with neuronal cell membranes to cause neuronal excitation and toxicity in fmole amounts. To determine the role of Tat in mediating HIV encephalitis (HIVE), we detected tat mRNA and protein in tissue extracts of nine patients with HIVE and seven patients without HIVE. Despite long autopsy times and significant degradation, tat mRNA was detected in 4/9 patients with HIVE but not in any of the seven patients without dementia. Similarly, the env mRNA was also detected in 5/9 patients with HIVE but not in the patients without HIVE. However, vif mRNA was detected in both groups of patients with (5/9) or without (2/7) HIVE. Using protein extracts from the brains of the same groups of patients we were unable to detect Tat by enzyme linked immunosorbant assay (ELISA) (sensitivity of 2 ng Tat/ml of brain tissue). However, Tat could be detected immunohistochemically and in protein extracts from the brains of rhesus macaques with encephalitis due to a chimeric strain of HIV and simian immunodeficiency virus (SHIV). Our observations support the role of Tat in the neuropathogenesis of HIV and SHIV encephalitis.

AIDS Dementia Complex↗
PubMed2000

Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine.

Human immunodeficiency virus type 1 (HIV-1) proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection. Recently, we showed the presence of Tat protein in brains of patients with HIV-1 encephalitis as well as macaques with encephalitis caused by a chimeric strain of HIV and simian immunodeficiency virus, and that even transient exposure of cells to Tat leads to release of cytopathic cytokines. Now, we report the first demonstration of gp120 protein in brain of patients with HIV encephalitis. We tested the hypothesis that Tat and gp120 would act synergistically to potentiate each protein's neurotoxic effects and determined the extent to which pharmacological antagonists against processes implicated in HIV-1 neuropathogenesis could block HIV-1 protein-induced neurotoxicity. Subtoxic concentrations of Tat and gp120, when incubated together, caused neuronal cell death and prolonged increases in levels of intracellular calcium. A transient exposure of neurons to Tat and gp120 for seconds initiated neuronal cell death, but maximal levels of neuronal cell death were observed with exposures lasting 30 minutes. The neurotoxicity caused by Tat and gp120 applied in combination was blocked completely by memantine, partially by amiloride, and not at all by dipyridamole or vigabatrin.

AIDS Dementia Complex↗
PubMed2000

Wound healing in the mitral valve.

BACKGROUND AND AIMS OF THE STUDY: Limited information is available on the healing of wounds in the mitral valve. In the present study, this process has been evaluated in young sheep. METHODS: Histologic, histochemical and transmission electron microscopic studies were made of the healing of wounds produced surgically under cardiopulmonary bypass, in the mitral valve (a 1 cm-long radially oriented incision at the free edge of the anterior leaflet) of young sheep (n = 11). RESULTS: All animals developed severe mitral regurgitation, as demonstrated by hemodynamic, ultrasound and ventriculographic studies. At four to five weeks, the edges of the incision were only partially covered by endothelium and had small deposits of fibrin. Two types of granulation tissue were associated with wound healing. The first covered the cut edge and consisted of myxoid tissue that extended from the valvular spongiosa and fibrosa; the second type consisted of spindle-shaped cells arranged parallel to the surface and surrounded by a slightly myxoid stroma. This granulation tissue resembled that caused by reactive fibrosis in regurgitant mitral valves. The connective tissue cells in granulation tissue developed increasing amounts of actin-like filaments as a function of time after operation. This differentiation resulted in the development of myofibroblasts. In contrast to the avascular nature of normal mitral leaflets, capillaries and arterioles first appeared in the middle portion of the leaflet at eight weeks, and at the proximal edges of the wounds at 12 weeks. CONCLUSION: The healing of mitral valvular wounds is a slow process that requires between eight and 12 weeks for the formation of a dense collagenous scar at the edges and complete restoration of the endothelial lining. Progression of healing is associated with the phenotypic modulation of connective tissue cells from fibroblasts to myofibroblasts and neovascularization of the leaflets.

Connective Tissue↗
PubMed2000

Natural rubber latex aeroallergen exposure in rubber plantation workers and glove manufacturers in Thailand and health care workers in a UK hospital.

OBJECTIVES: To estimate personal airborne natural rubber latex (NRL) concentrations for three occupational exposure groups; rubber plantation workers and NRL glove manufacturers in Thailand and health care workers in the UK. To utilise these data to classify the populations into appropriate exposure groups for the exposure-response analysis in the epidemiological study on latex allergy. METHODS: Two rubber plantations (110 workers), three NRL glove manufacturing factories (583 workers) in Thailand and one UK hospital (490 workers) were selected for the study. A preliminary workplace survey was carried out at each workplace in order to assign job titles subjectively in to high, moderate or low exposure groups for the purpose of sample selection. Between 5 and 20% of workers from each group for the three populations were then selected randomly for personal measurement of latex airborne allergens. Personal sampling was conducted using a 25 mm PTFE filter loaded in to an IOM sampling head at 2 l. min(-1). NRL aeroallergens were measured by an inhibition assay with NRL-specific IgE antibodies from NRL-sensitised people. RESULTS: A total of twenty-two personal samples were collected from plantation workers, sixty-one samples from the glove manufacturer employees and twenty seven from health care workers. The highest geometric mean (GM) NRL aeroallergen concentration was found in the glove manufacturing factories (7.3 microg m(-3)), followed by the rubber plantations (2.4 microg m(-3)) and the UK hospital (0.46 microg m(-3)). Amongst the NRL glove factories, the NRL aeroallergen concentrations were highest for those conducting the following tasks; glove stripping, glove inspections and packing of powdered gloves. The GM NRL aeroallergen for these tasks were in the range of 12.9 to 17.8 microg m(-3). CONCLUSIONS: In the process from tapping and manufacture of latex gloves through to their use the highest exposure to NRL aeroallergens is likely to occur in the manufacturing factories. Exposure to aeroallergens for the plantation workers was considered to be moderate and that of health care workers to be low.

Agriculture↗
PubMed2000

Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development.

p38alpha MAP kinase is activated in response to many cellular stresses and also regulates the differentiation and/or survival of various cell types in vitro, including skeletal muscle cells and cardiomyocytes. Here we show that targeted inactivation of the mouse p38alpha gene results in embryonic lethality at midgestation correlating with a massive reduction of the myocardium and malformation of blood vessels in the head region. However, this defect appears to be secondary to insufficient oxygen and nutrient transfer across the placenta. When the placental defect was rescued, p38alpha(-/-) embryos developed to term and were normal in appearance. Our results indicate that p38alpha is required for placental organogenesis but is not essential for other aspects of mammalian embryonic development.

Animals↗
PubMed2000

An evaluation of the management of patients with sore throats by practice nurses and GPs.

BACKGROUND: Practice nurses are increasingly involved in the management of minor illnesses in primary care. However, there has been little work published that evaluates the quality of the service they offer to patients. In our practice (semi-rural, 14,000 patients) a nursing triage system for minor illnesses has been established since 1992. AIM: To compare the quality of management of sore throats by practice nurses and general practitioners (GPs) in a routine nursing triage system. METHOD: An observational study assessing all patients over the age of two years presenting over a six-month period (February-August 1997) to either the practice nurse or GP with a sore throat as the chief presenting complaint. Patients were followed up at five to seven days by a researcher and recovery rates, analgesic requirements, reconsultation rates, and satisfaction rates were recorded. Patients who were still symptomatic at five to seven days were followed up again at 28 days and outcomes recorded. RESULTS: A total of 44% of patients consulted the practice nurse and 56% consulted the GP. Severity of presenting illness was similar in the two groups. The number of patients whose sore throats had settled, reconsultation rates, antibiotic prescription, and dissatisfaction rates were the same for both groups. However, the patients consulting the nurse had a more favourable outcome on indices such as patients' perception of being back to normal health (64% versus 53%) and median number of days for the sore throat to settle (four versus five). Nurses tended to see younger patients (mean age = 22.5 years versus 28.3 years) and more patients seeing the practice nurse recalled receiving advice about home remedies (76% versus 54%). CONCLUSION: Practice nurses can establish a safe and effective service for treatment of sore throats in a time-restricted triage system.

Adult↗
PubMed2000

Impact of temporal resolution on flow quantification by real-time 3D color Doppler echocardiography: numerical modeling and animal validation study.

Real-time, 3D color Doppler echocardiography (RT3D) is capable of quantifying flow at the LV outflow tract (LVOT). However, previous works have found significant underestimation for flow rate estimation due to finite scanning time (ST) of the color Doppler. The authors have, therefore, developed a mathematical model to correct the impact of ST on flow quantification and validated it by an animal study. Scanning time to cover the entire cross-sectional image of the LVOT was calculated as 60 ms, and the underestimation due to temporal averaging effect was predicted as 18 +/- 7%. In the animal experiment, peak flow rates were obtained by spatially integrating the velocity data front the cross-sectional color images of the LVOT. By applying a correction factor, there was an excellent agreement between reference flow rate by an electromagnetic flow meter and RT3D (angstroms=-5.6 ml/s, r=0.93), which was significantly better than without correction (p<0.001). Real-time, color 3D echocardiography was capable of quantifying flow accurately by applying the mathematical correction.

Animals↗
PubMed1999

Real-time three-dimensional echocardiography for measurement of left ventricular volumes.

Left ventricular (LV) volumes are important prognostic indexes in patients with heart disease. Although several methods can evaluate LV volumes, most have important intrinsic limitations. Real-time 3-dimensional echocardiography (RT3D echo) is a novel technique capable of instantaneous acquisition of volumetric images. The purpose of this study was to validate LV volume calculations with RT3D echo and to determine their usefulness in cardiac patients. To this end, 4 normal subjects and 21 cardiac patients underwent magnetic resonance imaging (MRI) and RT3D echo on the same day. A strong correlation was found between LV volumes calculated with MRI and with RT3D echo (r = 0.91; y = 20.1 + 0.71x; SEE 28 ml). LV volumes obtained with MRI were greater than those obtained with RT3D echo (126 +/- 83 vs 110 +/- 65 ml; p = 0.002), probably due to the fact that heart rate during MRI acquisition was lower than that during RT3D echo examination (62 +/- 11 vs 79 +/- 16 beats/min; p = 0.0001). Analysis of intra- and interobserver variability showed strong indexes of agreement in the measurement of LV volumes with RT3D echo. Thus, LV volume measurements with RT3D echo are accurate and reproducible. This technique expands the use of ultrasound for the noninvasive evaluation of cardiac patients and provides a new tool for the investigational study of cardiovascular disease.

Adult↗
PubMed1999

Association of a syndrome resembling Wegener's granulomatosis with low surface expression of HLA class-I molecules.

BACKGROUND: Granulomatous syndromes, such as Wegener's granulomatosis, are defined according to complex criteria, but the underlying cause is rarely identified. We present evidence for a new aetiology for chronic granulomatous lesions associated with a recessive genetic defect, which is linked to the human leucocyte antigen (HLA) locus. METHODS: Five adults with necrotising granulomatous lesions in the upper respiratory tract and skin, associated with recurrent bacterial respiratory infections and skin vasculitis, were identified. A diagnosis of Wegener's granulomatosis was considered in all of them, but abandoned because of an incompatible disease course and resistance to immunosuppressive treatments. Peripheral-blood samples were taken and analysed by immunohistochemistry and fluorescent-activated-cell-sorter analysis. Since all five patients were homozygous for the HLA locus, we looked for genetic defects located within the HLA-locus with PCR and restriction fragment length polymorphism. FINDINGS: A severe decrease in cell-surface expression of HLA class-I molecule was seen in all patients. Defective expression of the transporter associated with antigen presentation (TAP) genes was responsible for the HLA class-I down-regulation, and in two patients we identified a mutation in the TAP2 gene responsible for the defective expression of the TAP complex. We showed the presence of autoreactive natural killer (NK) cells and gammadelta T lymphocytes in the peripheral blood cells of two patients. Correction of the genetic defect in vitro restored normal expression of HLA class-I molecules and prevented self-reactivity in the patients' cells. Histology of granulomatous lesions showed the presence of a large proportion of activated NK cells. INTERPRETATION: Our findings define the cause and pathogenesis of a new syndrome that affects patients with a defective surface expression of HLA class-I molecules. The syndrome resembles Wegener's granulomatosis both clinically and histologically. Patients have chronic necrotising granulomatous lesions in the upper respiratory tract and skin, recurrent infections of the respiratory tract, and skin vasculitis. A predominant NK population within the granulomatous lesions suggests that the pathophysiology of the skin lesions may relate to the inability of HLA class-I molecules to turn off NK cell responses. Accurate genetic analysis of a defined syndrome can provide a better understanding of the cause and pathogenesis of a disease.

ATP-Binding Cassette Transporters↗