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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 37 records · Page 2Linked to original sources

The conserved N-terminal region of the mitotic checkpoint protein BUBR1: a putative TPR motif of high surface activity.

BUBR1, a key component of the mitotic spindle checkpoint, is a multidomain protein kinase that is activated in response to kinetochore tension. Although BUB1 and BUBR1 play an important role in cell division, very little is known about their structural characteristics. We show that the conserved N-terminal region of BUBR1, comprising residues 1-204, is a globular domain of high alpha-helical content ( approximately 60%), stable in the pH range 4-9 and probably organized as a tetratricopeptide motif repeat (TPR), most closely resembling residues 16-181 of protein phosphatase 5. Because the latter presents a continuous amphipathic groove and is regulated by binding certain fatty acids, we compared the properties of BUBR1(1-204) and TPR-PP5(16-181) at air/water interfaces and found that both proteins exhibited a similar surface activity and formed stable, rigid monolayers. The deletion of a region that probably comprises several alpha-helices of BUBR1 indicates that long-range interactions are essential for the stability of the N-terminal domain. The presence of the putative TPR motif strongly suggests that the N-terminal domain of BUBR1 is involved in direct protein-protein interactions and/or protein-lipid interactions.

Amino Acid Motifs↗

The amplitude of Mmax in human wrist flexors varies during different muscle contractions despite constant posture.

The amplitude of the maximal direct motor response (Mmax) elicited by supramaximal peripheral nerve stimulation can vary with time and with changes in muscle length. We sought to investigate the variability in the amplitude of Mmax in the human wrist flexors (flexor carpi radialis, FCR) at a constant joint position during different functional tasks. The subjects performed isometric wrist extension, radial deviation and gripping contractions matching either 10% or 50% of the EMG activity recorded in the extensor carpi radialis brevis (ECRB) during a wrist extension maximal voluntary contraction (MVC). Three supramaximal stimuli were delivered to the median nerve near the elbow during each task with 2-3 s between stimuli. Considerable variation was observed in the Mmax amplitude between the six tasks for individual subjects (coefficient of variation (CV) range, 6.0-31.4%). There was significantly greater variability between tasks at 50% MVC than at 10% MVC (p = 0.017). However, there were no systematic differences in Mmax amplitude between the six tasks across the group (p > 0.05). These results suggest that the amplitude of Mmax cannot be assumed as constant during experiments involving voluntary contractions even when subjects maintain the same posture.

Action Potentials↗

The crescent sign: dissociation of the polyethylene liner from a modular acetabular component in total hip arthroplasty.

OBJECTIVE: To study whether there was a common pattern of clinical symptoms, signs and radiographic features for the dissociation of the polyethylene liner from an acetabular component and to postulate reasons for these features. DESIGN AND PATIENTS: Retrospective study of notes and radiographs of cases of revision hip arthroplasty for polyethylene liner dissociation of the cementless Harris-Galante I porous-coated acetabular component (Zimmer Inc, Warsaw, IN) at the Avon Orthopaedic Centre, Bristol, UK and St. Mary's Hospital, Bristol, UK between 1995 and 2004. Patients were contacted to confirm preoperative symptoms. RESULTS: Nine cases of late polyethylene liner dissociation of this prosthesis have been revised in these institutions. All patients presented with a reduction in mobility, groin pain and limp. Eight patients reported an audible noise on hip movement. In all cases, radiographs showed radiolucency medial to the femoral neck in association with an eccentrically placed femoral head showing contact with the acetabular metal shell, which we have termed the "crescent sign." CONCLUSIONS: There is a typical clinical presentation in this study. The diagnosis can be made from a single anteroposterior pelvic radiograph without the need for previous films for comparison, or the need for arthrography. Clinicians should look specifically for the crescent sign when an eccentrically placed femoral head has been noted, in order to differentiate the more unusual diagnosis of dissociation from that of polyethylene wear. Early revision surgery can prevent damage to the femoral head and metal acetabular shell, thus reducing the complexity of revision surgery.

Adult↗

The Singaporean response to the SARS outbreak: knowledge sufficiency versus public trust.

During the outbreak of severe acute respiratory syndrome (SARS) in Singapore from 1 March to 11 May 2003, various national prevention and control measures were undertaken to control and eliminate the transmission of the infection. During the initial period of the epidemic, public communication was effected through press releases and media coverage of the epidemic. About a month into the epidemic, a public education campaign was mounted to educate Singaporeans on SARS and adoption of appropriate behaviours to prevent the spread of the disease. A survey was conducted in late April 2003 to assess Singaporeans' knowledge about SARS and infection control measures, and their concerns and anxiety in relation to the outbreak. The survey also sought to assess their confidence in the ability of various institutions to deal with SARS and their opinion on the seemingly tough measures enforced. The study involved 853 adults selected from a telephone-sampling frame. Stratified sampling was used to ensure adequate representation from major ethnic groups and age groups. The study showed that the overall knowledge about SARS and control measures undertaken was low (mean per cent score of 24.5 +/- 8.9%). While 82% of respondents expressed confidence in measures undertaken by Tan Tock Seng Hospital (the hospital designated to manage SARS), only 36% had confidence in nursing homes. However, >80% of the public agreed that the preventive and control measures instituted were appropriate. Despite the low knowledge score, the overall mean satisfaction score of the government's response to SARS was 4.47 (out of possible highest score of 5.00), with >93% of adult Singaporeans indicating that they were satisfied or very satisfied with the government's response to SARS. Generally, Singaporeans had a high level of public trust (satisfaction with government, confidence in institutions, deeming government measures appropriate), scoring 11.4 out of possible maximum of 14. The disparity between low knowledge on the one hand and high confidence and trust in the actions of the government on the other suggests that Singaporeans do not require high knowledge sufficiency to be confident in measures undertaken by the government to control the SARS crisis.

Adult↗

Quantitative trait loci for cell-wall components in recombinant inbred lines of maize (Zea mays L.) I: stalk tissue.

Maize silage is a significant energy source for animal production operations, and the efficiency of the conversion of forage into animal mass is an important consideration when selecting cultivars for use as feed. Fiber and lignin are negatively correlated with digestibility of feed, so the development of forage with reduced levels of these cell-wall components (CWCs) is desirable. While variability for fiber and lignin is present in maize germplasm, traditional selection has focused on the yield of the ear rather than the forage quality of the whole plant, and little information is available concerning the genetics of fiber and lignin. The objectives of this study were to map quantitative trait loci (QTLs) for fiber and lignin in the maize stalk and compare them with QTLs from other populations. Stalk samples were harvested from 191 recombinant inbred lines (RILs) of B73 (an inbred line with low-to-intermediate levels of CWCs) x De811 (an inbred line with high levels of CWCs) at two locations in 1998 and one in 1999 and assayed for neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL). The QTLs were detected on nine chromosomes, mostly clustered in concordance with the high genetic correlations between NDF and ADF. Adjustment of NDF for ADF and ADF for ADL revealed that most of the variability for CWCs in this population is in ADF. Many of the QTLs detected in this study have also been detected in other populations, and several are linked to candidate genes for cellulose or starch biosynthesis. The genetic information obtained in this study should be useful to breeding efforts aimed at improving the quality of maize silage.

Breeding↗

Controlled trial of interventions to increase testing and treatment for Helicobacter pylori and reduce medication use in patients with chronic acid-related symptoms.

BACKGROUND: Many symptomatic patients take proton pump inhibitors or histamine-2 blockers for years and those without gastro-oesophageal reflux disease might benefit from Helicobacter pylori eradication. AIM: To increase testing and treatment of H. pylori and reduce chronic use of proton pump inhibitors and histamine-2 blockers. METHODS: We conducted a three-armed controlled trial in 14 managed care practices. We included adults who used proton pump inhibitors or histamine-2 blockers for >1 year and excluded those with gastro-oesophageal reflux disease or previous endoscopy. We compared usual care (n = 312 patients from 6 practices) to low-intensity (n = 147 from 3 practices) and high-intensity (n = 122 from 5 practices) interventions. Low-intensity intervention consisted of guidelines, patient-lists, and a "toolkit"; high-intensity intervention added academic group detailing by a gastroenterologist with reinforcement by pharmacists. RESULTS: Compared with usual care, the high-intensity intervention increased H. pylori test-ordering (29% versus 9% at 12 months, P = 0.02). About half (23 of 58) of patients tested positive and 22 received eradication treatments. The high-intensity intervention decreased proton pump inhibitor use by 9% per year (P = 0.028), but did not alter histamine-2 blocker use. The low intensity intervention was ineffective. CONCLUSIONS: Providing guidelines, patient-lists, and toolkits was no better than usual care. Adding group detailing and pharmacist reinforcements led to improvements in H. pylori management and decreases in proton pump inhibitor use.

Adolescent↗

A lump in the throat: Should speech and language therapists treat globus pharyngeus?

PURPOSE: The causes of the feeling of a lump in the throat (globus pharyngeus) are disputed. The symptoms are persistent and may lead clients to change their diet and suffer a reduced quality of life. Coexisting swallowing difficulties are often reported but no neurological or structural abnormality can be found. Psychological factors are likely to play a part in the condition and an eclectic approach to therapy appears to be warranted. This paper reports on a treatment programme that includes education, reassurance and the use of exercises. METHOD: Fourteen clients participated. Their progress was assessed using the Glasgow and Edinburgh Throat Scale (GETS). A baseline period was used to assess the stability of their symptoms prior to therapy. This was followed by a group therapy session, use of the exercises and a further reassessment. Videofluoroscopy was conducted before and after therapy. RESULTS: Clients score on the GETS improved. However, change was seen both during the baseline and the treatment making it unclear which aspects of the treatment were effective. Improvement during the baseline suggests that clients benefit from attention and reassurance. It is unclear, therefore, whether the therapy session and the exercises provide a specific benefit or a general benefit due to continued attention. The clients' videofluoroscopies were unchanged after therapy. The presence of residue after the swallow in the valleculae and the pyriform sinuses may contribute to the symptoms of globus. CONCLUSION: The treatment is economical and appears to benefit clients. However, further research is needed to distinguish whether it has a specific effect or whether clients benefit from general attention and reassurance.

Adult↗

Diffuse pigmented villonodular synovitis of the foot and ankle treated with surgery and radiotherapy.

We followed up seven patients with histologically confirmed diffuse pigmented villonodular synovitis in a prospective study between 1992 ans 2001. The mean age at diagnosis was 30.7 years. The patients underwent synovectomy, followed by radiotherapy with a total dose of 35 Gy in 20 fractions. In all cases, the excision was considered incomplete when examined histologically. At an average follow up of 24 (18-36) months, six patients reported better function and reduced levels of pain. One patient remained symptomatic but did not have a recurrence. We conclude that a combined approach to a primary pigmented villonodular synovitis of the foot and ankle may reduce the risk of recurrence without functional impairment.

Adult↗

Small gastrointestinal stromal tumours with focal areas of low attenuation on CT: pathological correlation.

AIM: To describe the pathology of focal areas of low attenuation in small gastrointestinal stromal tumours on contrast-enhanced computed tomography (CT), and to investigate the association of these areas as predictors of malignant potential. MATERIALS AND METHODS: Contrast-enhanced helical CT images were obtained of 39 small (up to 5 cm) gastrointestinal stromal tumours. Focal areas of low attenuation were retrospectively evaluated and correlated with histopathological findings. The relation between the mitotic rate of and the presence of focal areas of low attenuation in the tumours was analyzed using Fisher's exact test. RESULTS: Of the 39 small gastrointestinal stromal tumours, 15 contained focal areas of low attenuation on CT. These were found to be due to solid tumour (n=5), haemorrhage (n=3), haemorrhage with necrosis (n=2), cystic degeneration (n=2), fluid in ulcer (n=2), and fibrous septum (n=1); they were not found to be associated with a high mitotic rate (p=0.45). CONCLUSION: Focal areas of low attenuation on CT in small gastrointestinal stromal tumours represent varying pathological conditions and do not predict malignant potential.

Adult↗

Neuronal nicotinic acetylcholine receptor subunits in autism: an immunohistochemical investigation in the thalamus.

The cholinergic system has been implicated in the development of autism on the basis of neuronal nicotinic acetylcholine receptor (nAChR) losses in cerebral and cerebellar cortex. In the present study, the first to explore nAChRs in the thalamus in autism, alpha4, alpha7 and beta2 nAChR subunit expression in thalamic nuclei of adult individuals with autism (n=3) and age-matched control cases (n=3) was investigated using immunochemical methods. Loss of alpha7- and beta2- (but not alpha4-) immunoreactive neurons occurred in the paraventricular nucleus (PV) and nucleus reuniens in autism. Preliminary results indicated glutamic acid decarboxylase immunoreactivity occurred at a low level in PV, co-expressed with alpha7 in normal and autistic cases and was not reduced in autism. This suggested loss of neuronal alpha7 in autism is not caused by loss of GABAergic neurons. These findings indicate nicotinic abnormalities that occur in the thalamus in autism which may contribute to sensory or attentional deficits.

Adult↗

Non-nicotine pharmacotherapies for smoking cessation.

International chronic obstructive pulmonary disease guidelines recommend that smokers be strongly advised to quit, and should be offered help in doing so. The most effective smoking-cessation interventions combine behavioural support with pharmacotherapies. For smokers who do not wish to use nicotine replacement treatments, bupropion is a safe and effective non-nicotine alternative first-line treatment. Nortriptyline and clonidine have demonstrated efficacy in aiding smoking cessation, but are regarded as second-line therapies. A number of other non-nicotine treatments show promise, but more data are required before these can be recommended in assisting smokers to stop.

Adrenergic alpha-Agonists↗

Genotoxicity evaluation of electromagnetic fields generated by 835-MHz mobile phone frequency band.

It is still unclear whether the exposure to electromagnetic fields (EMFs) generated by mobile phone radiation is directly linked to cancer. We examined the biological effects of an EMF at 835 MHz, the most widely used communication frequency band in Korean CDMA mobile phone networks, on bacterial reverse mutation (Ames assay) and DNA stability (in vitro DNA degradation). In the Ames assay, tester strains alone or combined with positive mutagen were applied in an artificial mobile phone frequency EMF generator with continuous waveform at a specific absorption rate (SAR) of 4 W/kg for 48 h. In the presence of the 835-MHz EMF radiation, incubation with positive mutagen 4-nitroquinoline-1-oxide and cumene hydroxide further increased the mutation rate in Escherichia coli WP2 and TA102, respectively, while the contrary results in Salmonella typhimurium TA98 and TA1535 treated with 4-nitroquinoline-1-oxide and sodium azide, respectively, were shown as antimutagenic. However, these mutagenic or co-mutagenic effects of 835-MHz radiation were not significantly repeated in other relevant strains with same mutation type. In the DNA degradation test, the exposure to 835-MHz EMF did not change the rate of degradation observed using plasmid pBluescript SK(+) as an indicator. Thus, we suggest that 835-MHz EMF under the conditions of our study neither affected the reverse mutation frequency nor accelerated DNA degradation in vitro.

4-Nitroquinoline-1-oxide↗

The reliability and validity of patient self-rating of their own voice quality.

OBJECTIVES: To provide preliminary data on the reliability and validity of dysphonic patients rating their own voice quality. DESIGN: Prospective reliability/validity assessment of voice ratings in dysphonic patients. SETTING: The Royal Free Hampstead NHS Primary Care Trust. PARTICIPANTS: Thirty-five adult dysphonia patients recruited from ENT referrals to a speech and language therapy department. Exclusion criteria were (i) a hearing impairment which may affect auditory discrimination and (ii) a diagnosis of cognitive impairment which may affect task comprehension. MAIN OUTCOME MEASURES: Patient intra-rater reliability was assessed by test-retest ratings, using G (Grade), R (Rough), B (Breathy), A (Asthenic), S (Strained) (GRBAS). Validity was assessed by comparing (i) patient-clinician inter-rater reliability, (ii) patients' GRBAS ratings with their Vocal Performance Questionnaire (VPQ) responses. RESULT: (i) Patients had lower intrarater reliability than clinicians (for G of GRBAS, kappa = 0.51 versus 0.74); (ii) patients consistently rated their voices more severely than clinicians (for G of GRBAS, mean rating = 1.4 versus 1.0); (iii) clinician-patient inter-rater agreement was no better than chance (paired t-test, all P < 0.05); (iv) patient ratings correlated significantly with vocal performance scores (r > 0.4, P < 0.05). CONCLUSIONS: Patients appear to have good validity and consistency using GRBAS as a self-perception tool. However, validity measured in terms of agreement with clinician ratings is poor. Voice patients may rate what they perceive rather than what they hear. Disagreement between patient and clinician ratings has implications for therapy aims, prognosis, patient expectations and outcomes. Where disagreement persists, the clinician may have to determine whether therapy priorities need redesigning to reflect patients' perceived needs, or to evaluate whether patient perceptions and expectations are unrealistic.

Adult↗

Real time magnetic resonance guided endomyocardial local delivery.

OBJECTIVE: To investigate the feasibility of targeting various areas of left ventricle myocardium under real time magnetic resonance (MR) imaging with a customised injection catheter equipped with a miniaturised coil. DESIGN: A needle injection catheter with a mounted resonant solenoid circuit (coil) at its tip was designed and constructed. A 1.5 T MR scanner with customised real time sequence combined with in-room scan running capabilities was used. With this system, various myocardial areas within the left ventricle were targeted and injected with a gadolinium-diethylenetriaminepentaacetic acid (DTPA) and Indian ink mixture. RESULTS: Real time sequencing at 10 frames/s allowed clear visualisation of the moving catheter and its transit through the aorta into the ventricle, as well as targeting of all ventricle wall segments without further image enhancement techniques. All injections were visualised by real time MR imaging and verified by gross pathology. CONCLUSION: The tracking device allowed real time in vivo visualisation of catheters in the aorta and left ventricle as well as precise targeting of myocardial areas. The use of this real time catheter tracking may enable precise and adequate delivery of agents for tissue regeneration.

Animals↗

Phenotypic variability in a Chinese family with rimmed vacuolar distal myopathy.

BACKGROUND: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene mutations have been found in patients with distal myopathy with rimmed vacuoles (DMRV). It is not clear how the same GNE gene mutations can result in different phenotypes in the same family with DMRV. METHODS: The clinical, neurophysiological, histopathological, and genetic characteristics of two patients with DMRV from a Chinese family from Taiwan were investigated. RESULTS: Two novel compound heterozygous mutations in different domains of the protein, Ile241Ser in the epimerase and Trp513stop in the kinase domain, were detected in both patients. However, the two patients demonstrated different patterns of disease progression: one had slow disease progression with a typical feature of DMRV (that is, weakness beginning in the distal leg muscles, typically anterior tibialis, with the quadriceps remaining relatively unaffected), and the other had rapid disease progression with an atypical presentation of DMRV. CONCLUSIONS: The results of the present study indicate that GNE gene mutations and probably modifier gene(s) or additional factors may result in different phenotypes of DMRV.

Adult↗

Relative atrophy of the flocculus and ocular motor dysfunction in SCA2 and SCA6.

Two hereditary ataxia syndromes show distinct profiles of region-specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin-2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze-holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin-2 mutations, and pursuit and gaze-holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze-holding are present in both conditions.

Adult↗

Cervical cystic hygroma/lymphangioma: an acquired idiopathic late presentation.

Lymphangiomas or cystic hygromas are relatively uncommon congenital malformations of the lymphatic system which usually present in the first years of childhood. Presentation in adult life is rare. We present a case of cervical adult cystic hygroma and discuss radiological and histopathological features as well as the management of these neck masses.

Aged↗