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Biomedical subjects

G Bell

Publications and source records attributed to G Bell.

At least 37 records · Page 2Linked to original sources

Effects of 16 weeks of resistance training on left ventricular morphology and systolic function in healthy men >60 years of age.

Resistance training (RT) has gained popularity as an effective form of exercise for older adults. However, the effects of RT on left ventricular (LV) morphology and systolic function in older persons is not well known. The purpose of this study was to assess the effects of 16 weeks of RT on LV morphology and systolic function in healthy older men. Subjects were randomly assigned into a RT group (n = 10; mean+/- SD age, 68 +/- 3 years) or a nonexercise control group (n = 10; age 68 +/- 4 years). RT was performed 3 times per week for 16 weeks at a mean intensity between 60% and 80% of 1 repetition maximum. Leg and bench press 1 repetition maximum and 2-dimensional echocardiography were performed at baseline and after 4, 8, 12, and 16 weeks of training in the RT group. Sixteen weeks of RT was associated with an increase in leg press maximal strength (baseline, 285 +/- 48 kg; after 16 weeks, 367 +/- 47 kg; p <0.05) and bench press maximal strength (baseline, 59 +/- 11 kg; after 16 weeks, 69 +/- 11 kg; p <0.05). No change in leg press maximal strength (baseline, 291 +/- 59 kg; after 16 weeks, 290 +/- 53 kg; p >0.05) or bench press maximal strength (baseline, 60 +/- 9 kg; after 16 weeks, 61 +/- 13 kg; p > .05) was found in control subjects during the same time. RT was not associated with changes in LV cavity size, wall thickness, mass, or systolic function after 4, 8, 12, and 16 weeks of exercise. Thus, 16 weeks of RT was sufficient to increase leg press and bench press maximal strength but did not alter the size or systolic function of the senescent left ventricle.

Aged↗

Purification of multiple heat shock proteins from a single tumor sample.

Heat shock protein-based vaccines have been shown to immunize against cancer and infectious diseases in both prophylactic and therapeutic protocols. So far, four classes of heat shock proteins (HSPs) preparation: gp96, HSP90 (hsp86, hsp84), HSP70 (hsc70, hsp70) and calreticulin have been used successfully. The methods for purifying them individually are now readily available. However, since tumors are not always available in large quantity, a major challenge remains the development of a procedure to simultaneously isolate these HSPs from the same sample. We report here that hsp40, hsp60, hsc70, hsp70, hsp84, hsp86, and gp96 (grp94) but not BiP (grp78) and calreticulin can be separated from a single tumor sample in one step using heparin-agarose chromatography. Interestingly this procedure separates the HSP70 isoforms hsp70 from hsc70, but not the HSP90 isoforms hsp84 and hsp86. The three main immunogenic HSPs, gp96, hsp86/84, and hsc70 can be further isolated to homogeneity using additional purification methods. In addition, we have shown that the interaction of the chaperoned peptides with hsc70 and gp96 is not compromised during heparin chromatography. These observations provide a new method for preparation of multiple HSP-based vaccines, circumventing the sample size limitation, as well as providing the possibility to study how multiple HSPs can synergize in eliciting immunity.

Animals↗

Effect of pH on rate of interfacial inactivation of serine proteases in aqueous-organic systems.

We studied the inactivation of trypsin and alpha- and beta-chymotrypsin by passage of droplets of tridecane though their aqueous solutions. The mechanism involves contact with the interface, because the loss of activity is proportional to the total area exposed. The rates of inactivation vary up to fivefold over the pH range 3 to 10. However, there is no clear maximum at the isoelectric point (pI) of each enzyme, where the amount of protein adsorbed is usually found to be highest. This is probably because, at the pI, there is also a minimum in structural alteration on adsorption. There may be a weak correlation with pH effects on foamability of the enzyme solutions, a parameter reported to reflect the "hardness" of different proteins, which controls their interfacial unfolding. The pH dependence of both inactivation and hardness cautions against attempts to correlate inactivation of different enzymes with a single value of a parameter such as adiabatic compressibility. There is no correlation between the effects of pH on interfacial inactivation and those reported in the literature on irreversible inactivation in concentrated urea or at high temperature.

Chymotrypsin↗

Mild environmental stress elicits mutations affecting fitness in Chlamydomonas.

Cultures of Chlamydomonas were exposed to a range of relatively mild stresses for a period of 24 h. These stresses comprised high and low temperatures, osmotic stress, low pH, starvation and toxic stress. They were then allowed to recuperate for around ten vegetative generations under near-optimal conditions in unmodified minimal medium. Fitness was then assayed as the rate of division of isolated cells on agar. We found that there was a strong tendency for stressed cultures to have lower mean fitness and greater standardized variance in fitness than the negative controls which had been cultured throughout in unmodified minimal medium. The same tendency was shown, as expected, by positive controls which received mutagenic doses of ultraviolet irradiation. We concluded that the most reasonable interpretation of these observations is that mild stress increases the genomic rate of mutation. This appears to be the first time that this phenomenon has been noticed in eukaryotes. The response might be adaptive because lineages in which higher mutation rates are elicited by stress can be favourably selected through the production of a few mutants which are fortuitously well adapted to the stressful environment. Other interpretations are not excluded, however. Regardless of the mechanism involved, the elevation of mutation rates under stress will affect the rate of evolutionary response to environmental change and also the maintenance of sexuality.

Animals↗

Apparent confined placental mosaicism of trisomy 16 and multiple fetal anomalies: case report.

Trisomy 16 is frequently found confined to the placenta (confined placental mosaicism (CPM)), with a structurally normal fetus. In some cases of trisomy 16, the fetus has uniparental disomy for chromosome 16 (UPD16) which is associated with intrauterine growth restriction (IUGR) and fetal anomalies. We report a case of apparent confined placental mosaicism for trisomy 16, using standard cytogenetic techniques, but with multiple fetal abnormalities including congenital diaphragmatic hernia in which there was no evidence of UPD in the disomic tissues examined. Subsequent examination of fetal tissues using fluorescent in situ hybridization (FISH) demonstrated low levels of mosaicism for trisomy 16 in all the tissues examined. The use of FISH permits identification of mosaicism which conventional techniques may not identify.

Abnormalities, Multiple↗

Hepatitis A in New South Wales, Australia from consumption of oysters: the first reported outbreak.

Between 22 January and 4 April 1997, 467 hepatitis A cases were reported to the New South Wales Health Department, Australia. To identify the cause of the outbreak, we conducted a matched case-control study, and an environmental investigation. Among 66 cases and 66 postcode-matched controls, there was a strong association between illness and consumption of oysters (adjusted odds ratio 42; 95 % confidence interval 5-379). More than two-thirds of cases reported eating oysters, including one third of cases and no controls who reported eating oysters in the Wallis Lake area. A public warning was issued on 14 February, and Wallis Lake oysters were withdrawn from sale. Hepatitis A virus was subsequently identified in oyster samples taken from the lake. Hepatitis A virus poses a special risk to consumers who eat raw oysters because it can survive for long periods in estuaries and cause severe disease.

Adult↗

Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH.

In man high levels of aneuploidy are seen in spontaneous abortions. Very few autosomal trisomies survive to birth, the three most common being those for chromosome 13, 18 and 21 giving rise to the syndromes named Patau, Edwards and Down respectively. Since the majority of these spontaneously abort, what makes the survivors different from the aborters? Could it be that they have tissue specific mosaicism with the additional normal cell line supporting survival? In this study fluorescence in situ hybridisation was used as a convenient way to detect trisomy in interphase cells. To study the level of mosaicism across gestation, different tissues from 21 trisomic foetuses were analysed using probes for chromosome 13, 18, 21, X and Y. Two trisomy 18 foetuses exhibited mosaicism. Two others, one trisomy 13 and one trisomy 18 had mosaic placentas. There was no clear association between the limited mosaicism seen and severity of the phenotype. We conclude that at least for this sample set, tissue-specific mosaicism was not likely to be responsible for potential survival to birth.

Adult↗

Patients' perspectives on services for epilepsy: a survey of patient satisfaction, preferences and information provision in 2394 people with epilepsy.

The objectives of this study were to provide a comprehensive survey of satisfaction with care, care preferences and information provision for patients with epilepsy, and to formulate recommendations for the development of epilepsy services based on the findings. A questionnaire was distributed to 4620 patients who were currently receiving antiepileptic drugs for epilepsy, regardless of aetiology, duration or severity. Two different samples of patients with epilepsy were questioned: the first an unselected sample drawn from primary care, and the second consisting of consecutive patients drawn from hospital clinics. There were 2394 responses to the questionnaire. Satisfaction with primary and hospital care was high, both overall and for specific aspects. However, two major shortcomings were identified. First, few respondents felt that their care was shared between hospital and GP. Secondly, provision of information about epilepsy was perceived to be poor, particularly by the elderly. Younger patients and patients with severe epilepsy had a higher satisfaction with and preference for hospital care, whereas older age groups were more satisfied with and preferred primary care. Patients' main reasons for preferring primary care were that it was more personal and the GP was more familiar with them, and secondary care was preferred because the hospital doctor knew more about epilepsy. In conclusion, we have conducted the largest representative UK survey of patients' perceptions and views of the care available for epilepsy. Although patient satisfaction was high, information provision is poor and the shared care model is not operating effectively. We recommend that an emphasis be placed on methods for improving the interface between primary and secondary care. The setting up of hospital epilepsy centres, as recommended by the recently published Clinical Standards Advisory Group report on epilepsy, would provide a focus for these efforts and for information provision.

Adolescent↗

NHS services for epilepsy from the patient's perspective: a survey of primary, secondary and tertiary care access throughout the UK.

The aims of this study were to estimate the proportion of patients with epilepsy who made primary care and/or hospital outpatient medical consultations within 1 year; to formulate a model of the explanatory variables that influence whether patients consult or not; and to estimate the frequency of referral to, and waiting time for, hospital outpatient clinics in patients with new-onset seizures. Suggestions are offered for improvement of epilepsy services based on the findings. A questionnaire was distributed to 3455 unselected patients identified at population level from primary care practices in all NHS regions of the UK. There were 1652 respondents with epilepsy of all types, irrespective of aetiology, duration or severity. Fifty-two per cent of the whole sample made at least one medical consultation of any type specifically for epilepsy (42.0% primary care, 30.5% hospital, 20.4% both). Most patients with controlled epilepsy (74.5%) had no consultations. Of patients with severe epilepsy, 27.5% made no primary care consultations, 43.4% no hospital consultations and 14.1% no consultations of either type. Gender did not influence the likelihood of either GP or hospital consultations in patients with either controlled or active epilepsy. Increasing seizure frequency was associated with a greater likelihood of one or more hospital consultations for epilepsy, whereas increasing duration of epilepsy was associated with a decreased likelihood of either type of consultation. Age affected consultation rates: of those patients over the age of 65 years, only 29.9% made a medical consultation for epilepsy, compared to 53.8% of young adults. Patients under the age of 17 years were less likely to have consulted a GP and more likely to have consulted a hospital doctor. Ninety percent of new-onset patients had been referred to a hospital doctor, and the mean wait was 6.5 weeks. In conclusion, many patients with epilepsy, including severe epilepsy, are not receiving specialist input, and a significant proportion are receiving no medical supervision. The elderly are over-represented in this group. Care tends to be polarized between hospital or primary care, falling short of the ideal of shared care. It will be important to address the influences on consultation seeking in epilepsy, particularly for those patients currently under no medical supervision.

Adolescent↗

The ecology and genetics of fitness in Chlamydomonas. IX. The rate of accumulation of variation of fitness under selection.

Populations of Chlamydomonas founded by single cells were cultured in chemostats for 50 days, representing about 125 generations. The mean and variance of division rate was measured daily by withdrawing cells from the effluent and culturing them for 24 h on filtered effluent medium solidified with agar. Mean fitness did not change during the period of culture, and the behavior of neutral markers indicated that no substitutions of novel beneficial mutations occurred. However, the variance of fitness increased markedly at about the same rate in two replicate populations. The standardized rate, or mutational heritability, was Vm/VE = 4-5 x 10(-3) per generation. This is substantially greater than most other estimates for characters closely correlated with fitness. Moreover, it seems difficult to reconcile with the absence of any change in mean fitness. We investigated the possibility that frequency-dependent selection was created by spatial heterogeneity within the culture vessel by testing cell populations with different phenotypes from the top, bottom, and surface of the chemostats. However, the differentiation of these populations seemed to be attributable to phenotypic plasticity, with no evidence that their characteristics were heritable. Finally, we report an experiment in which lines were selected for about 100 generations on solid or liquid medium. These lines became specifically adapted to the medium on which they were cultured, showing that liquid and solid media, even when chemically identical, provide different conditions of growth for Chlamydomonas. The genetic variance appearing in the cultures was therefore attributed to conditionally neutral mutations that were not expressed in the chemostat. This implies that rates of accumulation of mutational variance measured in the culture environment itself (where this can be done) may greatly underestimate the variation available for a response through selection to environmental change. Moreover, it suggests that chemostat populations may be more dynamic and more diverse than is usually thought.

Animals↗

The ecology and genetics of fitness in Chlamydomonas. X. The relationship between genetic correlation and genetic distance.

A necessary condition for the maintenance of genetic variation in heterogeneous environments is that the relative fitnesses of a collection of genotypes vary as conditions of growth change. This can be detected by estimating the amount of gene-by-environment interaction (G x E) when a range of types are tested across a range of conditions. However it is the sign and magnitude of the genetic correlation, which is a component of G x E, that governs the ultimate fate of variation. Whether genetic variation will be preserved, then, depends on how the genetic correlation changes as a function of the ecological differences among environments and the genetic differences among genotypes. To evaluate this, we assayed the performance of 15 chlorophyte species of known genetic relation in 20 environments. We found that the quantity of G x E increased as both the environmental variance across environments and the genetic distance increased. Moreover the genetic correlation declined as the environmental variance between pairs of environments and the genetic distance between pairs of genotypes increased. These results suggest that divergent selection will be more likely to maintain genetic variation when environments are strongly contrasted and genotypes widely divergent.

Animals↗

Off-street sex workers and their use of genitourinary medicine services.

Our objective was to identify barriers to the use of genitourinary medicine (GUM) services for off-street female sex workers in a provincial city, using self-administered anonymous questionnaires distributed to premises during outreach sessions by a clinic health adviser. Questionnaires were completed by 85 (56%) of the estimated 150 women working in the 13 targeted premises. The main obstacles to service use were the length of time spent in clinic (83%), dislike of needles (28%), difficulty getting to clinic (18%) and dislike of examinations (16%). The majority (71%) rejected sex worker-only sessions. Women using the local service, which provided outreach sessions, were more likely to have disclosed their occupation to the service (82% vs 36%; P=0.035). GUM clinics may optimize their accessibility to sex workers by minimizing the time required per visit, and introducing non-invasive screening methods where possible. Outreach visits by clinic staff may encourage women to disclose their occupation, enabling them to assess vaccinations for hepatitis B.

Ambulatory Care Facilities↗

Functional electrical stimulation exercise increases GLUT-1 and GLUT-4 in paralyzed skeletal muscle.

The study purpose was to determine the effect of functional electrical stimulation (FES)-leg cycle ergometer training (30 minutes on 3 d/wk for 8 weeks) on the GLUT-1 and GLUT-4 content of paralyzed skeletal muscle. Biopsy samples of vastus lateralis muscle were obtained pre- and post-training from five individuals with motor-complete spinal cord injury ([SCI] four men and one woman aged 31 to 50 years, 3 to 25 years postinjury involving C5-T8). Western blot analysis indicated that GLUT-1 increased by 52% and GLUT-4 increased by 72% with training (P < .05). This coincided with an increase in the muscle oxidative capacity as indicated by a 56% increase in citrate synthase (CS) activity (P < .05) and an improvement in the insulin sensitivity index as determined from oral glucose tolerance tests (P < .05). It is concluded that FES endurance training is effective to increase glucose transporter protein levels in paralyzed skeletal muscle of individuals with SCI.

Adult↗

Histochemical changes in muscle of individuals with spinal cord injury following functional electrical stimulated exercise training.

STUDY DESIGN: Longitudinal training. OBJECTIVES: To determine the effects of functional electrical stimulated (FES) leg cycle ergometer training on muscle histochemical characteristics in individuals with motor-complete spinal cord injury (SCI). SETTING: University of Alberta, Edmonton, Alberta, Canada. METHODS: Six individuals with motor-complete SCI (age 31-50 years; 3-25 years post-injury) trained using FES leg cycle ergometry for 30 min, 3 days per week for 8 weeks. Biopsies of the vastus lateralis muscle were obtained pre- and post-training and analyzed for fibre composition, fibre size and capillarization. RESULTS: The majority of muscle fibres were classified as type 2 pre- and post-training. Average fibre area increased 23% (P<0.05) and capillary number increased 39% (P<0.05) with training. As a result of these proportional increases, capillarization expressed relative to fibre area was unchanged with training. CONCLUSIONS: FES leg cycle ergometer training results in proportional increases in fibre area and capillary number in individuals with SCI.

Adult↗

Massive bleeding during spine surgery in a patient with ankylosing spondylitis.

PURPOSE: Ankylosing spondylitis is associated with pathophysiology that has important anaesthetic implications. We report a case where the sequelae of ankylosing spondylitis may have been responsible for massive bleeding during emergency spine surgery. CLINICAL FEATURES: A 69 yr old man with long standing ankylosing spondylitis sustained a complex fracture of the lumbar spine in a fall, and was scheduled for stabilization of the spine. Under general anaesthesia, prone positioning was difficult because of the extreme spinal deformity. During exploration, dilatation of epidural veins was encountered and sustained haemorrhage was encountered throughout the surgical procedure. Estimated blood loss was 17,000 ml which was replaced with 31 units of packed red blood cells, 3200 ml of salvaged blood, 18 units of fresh frozen plasma, 26 units of platelets, 1,000 ml of albumin and 9,000 ml of crystalloid. CONCLUSIONS: Extreme deformity of the spine led to positioning difficulties that may have contributed to massive blood loss during complex spine surgery. Difficulties with placement in the prone position in-patients with advanced ankylosing spondylitis should be anticipated.

Aged↗