Biomedical subjects

J Ling

Publications and source records attributed to J Ling.

At least 19 recordsLinked to original sources

PubMed2000

The role of 5'-leader length, secondary structure and PABP concentration on cap and poly(A) tail function during translation in Xenopus oocytes.

The 5'-cap structure and poly(A) tail of eukaryotic mRNAs function synergistically to promote translation initiation through a physical interaction between the proteins that bind to these regulatory elements. In this study, we have examined the effect of leader length and the presence of secondary structure on the translational competence and the function of the cap and poly(A) tail for mRNAs microinjected into Xenopus oocytes. Increasing the length of the 5'-leader from 17 to 144 nt resulted in a 2- to 4-fold increase in expression from an mRNA containing an unstructured leader but increased expression up to 20-fold for an mRNA containing 5'-proximal structure. Consequently, the presence of secondary structure was less inhibitory for those mRNAs with a longer 5'-leader. Co-injection of poly(A)-binding protein (PABP) mRNA increased the function of the cap and poly(A) tail in promoting translation from poly(A)(+) but not poly(A)(-) mRNAs, particularly for mRNAs containing secondary structure. In the absence of an internal ribosome entry site, expression from the distal cistron of a dicistronic mRNA increased as a function of the length of the intercistronic region and the concentration of PABP. The inhibitory effect of intercistronic located secondary structure on translation was position-dependent. Indeed, the effect of secondary structure was abolished if positioned 134 nt upstream of the distal cistron. These data suggest that the length of a leader, the presence of secondary structure and the concentration of PABP determine the extent to which the cap and poly(A) tail regulate translation.

5' Untranslated Regions↗

PubMed2000

Stability of a varicella-zoster virus glycoprotein E epitope.

The epitope stability of a varicella-zoster virus (VZV) glycoprotein E (gE) was analyzed with monoclonal antibodies (mAbs) in cells infected with different passages of various VZV strains and isolates. The gE-specific mAbs recognized same antigenic sites (epitopes) in VZV isolates with various passage history. All VZV strains and virus-isolates reacted with an anti-gE monoclonal antibody by immunoprecipitation, or indirect fluorescent antibody staining test. Sera from VZV seropositive individuals reacted with a truncated VZV gE glycoprotein, designated TgpI-511. Also, human mononuclear cells (MNCs) stimulated with TgpI-511 glycoprotein were shown to produce VZV-specific antibodies in vitro. The results demonstrated the stability of these gE epitopes tested in this study in TgpI-511 and among the VZV-isolates obtained from different passages. These results also suggest that VZV glycoproteins as well as live attenuated or killed varicella vaccines containing these epitopes could be used as therapeutic booster vaccines in adults and the elderly to prevent zoster.

Adolescent↗

PubMed2000

Rethinking patient satisfaction: patient experiences of an open access flexible sigmoidoscopy service.

The high morbidity and mortality rates for colo-rectal cancer in Teesside, UK, have led to the initiation of an open access service in two local National Health Service Trust hospitals. This paper reports the results of a pilot patient satisfaction study of the service using a combination of participant-observation, in-depth interviews and questionnaire methods. Although offering a standardised service, ethnographic study revealed interesting differences in practice and follow-up procedures between the two hospitals. Patients, both verbally and on paper, expressed high levels of satisfaction with the services offered at both hospitals, yet in-depth, qualitative research revealed a more complex picture. The evidence from this research will be used to argue that standard consumer satisfaction questionnaires of health provision are inadequate indicators of patients' experience of health care delivery.

Adult↗

PubMed2000

What influences participation in clinical trials in palliative care in a cancer centre?

Like any other specialty, palliative care needs a scientific foundation on which to base its practice. Research in palliative care is particularly difficult because of the characteristics of the patient population under study (e.g. advanced disease, poor performance status and limited prognosis). The aim of this paper was to highlight the challenges of recruitment into clinical trials in palliative care. Information on all patients treated at a specialist cancer centre who were referred for consideration of entry into any one of 23 clinical trials in palliative care was collected prospectively over 4 years to determine factors that influence patients to accept or reject entry into a study. Of the 1206 patients referred, 558 (46%) met the entry criteria. Of these, 362 (30%) agreed to enter and 248 (21% of all those referred) completed the study. Thus, 65% of all eligible patients were entered into trials but only 44% of these completed the study. The relatively high percentage of patients entered probably reflects the site (a cancer centre with a high research profile) and is not typical of other palliative care centres or hospices. The most common reasons given for unwillingness to participate were a wish to defer to a later date, a deterioration in condition, distance from home to hospital, a lack of interest, transfer to another unit, inability to give consent and family objection. In order to maximise patient accrual into trials in palliative care, studies should be designed to suit the patient population under study (e.g. be of short duration with realistic entry criteria) and not necessarily mirror the trial methodology of therapeutic trials in oncology.

Adolescent↗

PubMed2000

The effect of a nonverbal aid on preschoolers' recall for color.

The purpose of the present study was to investigate whether the provision of a nonverbal memory aid would improve preschoolers' recall of color. Forty 4-year-old children carried out 2 tasks with the same set of colored objects. Colors were not referred to, nor were children told that their recall would later be tested. One day later, the children were split into 2 groups. One group was given a chart containing both the colors of the objects and distractor colors. The other group was not given a chart. Recall for object color was tested. There was an effect of chart provision; children who used the chart recalled more colors correctly than did those who did not use a chart. This result indicates (a) that even very young children can make use of props to facilitate their recall and (b) that such memory aids need not be exact copies of previously seen objects. Implications of these findings for eyewitness recall are discussed.

Child Behavior↗

PubMed2000

Immunolocalization analysis of transforming growth factor-beta1 in the growth plates of broiler chickens with high and low incidences of tibial dyschondroplasia.

Immunolocalization of transforming growth factor-beta1 (TGF-beta1) was determined in growth plates of two lines of broiler chickens with low and high incidences of tibial dyschondroplasia (TD). Ultrathin sections of growth plates from each line were treated with a polyclonal antibody specific for TGF-beta1, followed by colloidal gold-labeled protein A. Immunolocalization for TGF-beta1 was observed in chondrocytes of all zones of growth plates of low and high TD incidence lines. However, immunolocalization in extracellular matrix was restricted to the hypertrophic zones of both lines. In the hypertrophic zone of low TD incidence line, immunolocalization of TGF-beta1 in the extracellular matrix adjacent to collapsed cartilage canals (matrix streaks) was significantly greater than immunolocalization between patent cartilage canals. A similar increase was not observed in the high TD incidence line. Results indicate that chondrocytes of all zones of the growth plate contain TGF-beta1 but do not release it into extracellular matrix until hypertrophy has occurred. Greater concentrations of TGF-beta1 adjacent to collapsed cartilage canals may play a role in controlling angiogenesis and directing invasion of mineralized hypertrophic cartilage by metaphyseal blood vessels. A low concentration of TGF-beta1 in the extracellular matrix adjacent to collapsed cartilage canals of the high TD incidence line may be a factor in limiting vascular invasion of dyschondroplastic cartilage of TD lesions.

Animals↗

PubMed2000

Heat shock protein HSP101 binds to the Fed-1 internal light regulator y element and mediates its high translational activity.

The internal light-regulatory element (iLRE) of ferredoxin (Fed-1) mRNA, comprising the 5' leader and at least the first 13 codons of the open reading frame, controls transcript abundance after illumination of the plant in a translation-dependent manner. We have characterized the RNA binding activities associated with the Fed-1 iLRE and have identified one activity as the heat shock protein HSP101, a protein shown to bind the 5' leader of tobacco mosaic virus. HSP101 was sufficient and necessary to mediate a high level of translational activity from a Fed-1 iLRE-containing mRNA in yeast. Moreover, the Fed-1 iLRE substantially enhanced translation of reporter mRNAs in plant protoplasts expressing HSP101. Expression of HSP101 was subject to developmental regulation in leaves in that expression was highest in young leaves. These data suggest that Fed-1 mRNA may use the HSP101 regulatory mechanism as a means of ensuring a high level of translation required for the light-mediated regulation of Fed-1 mRNA stability.

Binding Sites↗

PubMed1999

Secondary structure in the 5'-leader or 3'-untranslated region reduces protein yield but does not affect the functional interaction between the 5'-cap and the poly(A) tail.

The 5'-cap structure and poly(A) tail of eukaryotic mRNAs cooperate to promote translation initiation but whether this functional interaction benefits certain classes of mRNAs has not been investigated. In this study, we investigate whether a structured 5'-leader or 3'-untranslated region (UTR) affects the cap/poly(A) tail interaction. A structured leader reduced the degree to which the 5'-cap promoted translation in plant cells and inhibited translation from capped and uncapped mRNAs equally in yeast. Secondary structure within the 3'-UTR reduced translational efficiency when adjacent to the stop codon but had little effect on the cap/poly(A) tail synergy. The functional interaction between the cap and poly(A) tail was as important for an mRNA with a structured leader or 3'-UTR as it was for an unstructured mRNA in either species, suggesting that these structures can reduce translation without affecting the functional interaction between the cap and poly(A) tail. However, the loss of Xrn1p, the major 5'-->3' exoribonuclease in yeast, abolished cap-dependent translation and the functional interaction between the cap and poly(A) tail, suggesting that the cap/poly(A) tail synergy is of particular importance under conditions of active RNA turnover.

3' Untranslated Regions↗

PubMed1999

Malignant astrocytoma cell attachment and migration to various matrix proteins is differentially sensitive to phosphoinositide 3-OH kinase inhibitors.

Phosphoinositide 3-OH kinase (PI3-K) has been shown to play an important role in the signaling pathway necessary for cytoskeletal reorganization in non-astrocytic cells. We investigated the role of PI3-K in U-251 MG human malignant astrocytoma cell adhesion and migration. Attachment of U-251 MG cells to vitronectin, fibronectin, laminin, and collagen was inhibited in a concentration-dependent manner by two specific inhibitors of PI3-K (Wortmannin and LY294002). Attachment to vitronectin, fibronectin, and laminin was more sensitive to inhibition of PI3-K (45% inhibition at 10 nM Wortmannin) than attachment to collagen (25% inhibition at 100 nM Wortmannin). Similarly, migration toward these substrates showed differential sensitivity to inhibition. Attachment of the cells to these matrix proteins resulted in an increase in PI3-K activity, as compared to that of cells in suspension, with attachment to vitronectin resulting in the greatest increase in PI3-K activity. p125 focal adhesion kinase (p125FAK) was found to co-immunoprecipitate with PI3-K from the NP40-soluble cell fraction of a 1% NP40 detergent lysate of cells in the early stages of adhesion to vitronectin and fibronectin, but not during adhesion to collagen. The expression of p125FAK protein and level of phosphorylation were similar on adherence to all three substrates. These data indicate that the sensitivity of U-251MG cell attachment and migration to PI3-K inhibitors is substrate-dependent, and that complex formation of PI3-K and p125FAK correlates with this sensitivity to PI3-K inhibitors. Our data suggest a role for PI3-K and p125FAK complex formation in PI3-K activation.

Astrocytoma↗

PubMed1999

Electromagnetic and thermal modeling of SAR and temperature fields in tissue due to an RF decoupling coil.

The finite difference time domain method is used to calculate the specific absorption rate (SAR) due to a butterfly surface coil in a realistic tissue model of the leg. The resulting temperature distribution and temperature changes are found using a finite difference solution to the bioheat transfer equation. Reasonable agreement is found between predicted temperature changes and those measured in vivo provided that the resulting hyperthermia does not induce noticeable changes in perfusion. The method is applicable to radiofrequency dosimetry problems associated with high Bo field magnetic resonance systems and where knowledge of spatial variation in SAR is important in assessing the safety of new magnetic resonance procedures.

Absorption↗

PubMed1999

The orthodontic treatment need and demand of Hong Kong Chinese children.

OBJECTIVE: To investigate the need and demand for orthodontic treatment of Chinese school children in Hong Kong. METHODS: The material consisted of study casts and questionnaires collected from 765 randomly selected 12-year-old school children in Hong Kong. The need for orthodontic treatment was assessed by the Index of Orthodontic Treatment Need, and questionnaires were used in assessing demand for orthodontic treatment. RESULTS: The results indicate that 12% of the 12-year-old school children had no need of orthodontic treatment, 18% had little need (Grade 2), 33% moderate need (Grade 3), 33% great need (Grade 4), and 4% of children had very great need for orthodontic treatment (Grade 5). About two thirds of the children were not satisfied with their dental appearance, but only 40% of these would like to have orthodontic treatment. A definite relationship was found between negative self-appraisal of dental appearance and demand for orthodontic treatment. CONCLUSION: The study demonstrates that the need of orthodontic treatment among Chinese children is similar to that of Caucasian children; the attitude and demand toward treatment are also similar.

Chi-Square Distribution↗

PubMed1998

DNA-cleaving activity of superoxide dismutase specific for circular supercoiled double-stranded DNA in vitro.

Several superoxide dismutases (SODs), N. tabacum Mn-SOD, porcine erythrocyte Cu/Zn-SOD and bovine erythrocyte Cu/Zn-SOD, have been found to exhibit the activity to cleave the circular supercoiled double-stranded DNA into nicked and further linear form in vitro. The fact that porcine erythrocyte Cu/Zn-SOD did not cleave the linear double-stranded DNA excluded the possibility that nuclease contaminated the SOD preparations and showing the cleaving activity was dependent on the supercoiled form of DNA. Porcine erythrocyte Cu/Zn-SOD inactivated by H2O2 or guanidine still remained its supercoiled DNA-cleaving activity. However, when the SOD was digested with proteases, its activity to cleave supercoiled DNA was completely abolished. These results suggested that the supercoiled DNA-cleaving activity was relative to the apoenzyme moiety, less relevant to the O2- dismutation site of SOD. The enzymatic mechanism of cleaving activity of SOD to supercoiled DNA was discussed.

Animals↗

PubMed1998

Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls.

Germ-line mutations in DNA mismatch-repair genes impart a markedly elevated cancer risk, often presenting as autosomal dominant hereditary nonpolyposis colorectal cancer (HNPCC). However, there are no pathognomonic features of HNPCC, not all gene carriers have a family history of the disease, and families fulfilling the Amsterdam criteria are relatively uncommon. Genetic testing of probands with early-onset colorectal cancer, irrespective of family history, is one approach that would allow predictive genetic testing of at-risk relatives. We cloned and sequenced hMSH2 and hMLH1 introns, to optimize genomic sequencing. We then systematically analyzed the entire hMSH2 and hMLH1 genes, by genomic sequencing and in vitro synthesized-protein-truncation assay (IVSP), in 50 colorectal cancer patients <30 years of age at diagnosis. To determine polymorphic variants, 26 anonymous donors also were sequenced. All subjects analyzed had at least 1 of 37 different polymorphic or pathogenic variants. IVSP complemented genomic sequencing, by detection of mutations not identified by genomic analysis. Fourteen cancer patients (28%) had pathogenic mutations, and a number of other variants also may have had a pathogenic significance that remains to be elucidated. Tumor replication-error status was useful in targeting sequencing efforts for this cohort of young patients: sensitivity was 86%, specificity 73%, and positive and negative predictive values 63% and 90%, respectively. These data indicate that an appreciable proportion of young colon cancer probands carry a germ-line mutation in a DNA mismatch-repair gene.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Impact of femoro-distal bypass on major lower limb amputation rate.

BACKGROUND: Limb salvage is one of the cardinal aims of vascular surgery, but the influence of distal bypasses on amputation rates has been difficult to demonstrate. METHODS: The incidence and indications for major limb amputations and infrapopliteal bypass during two consecutive 16-month periods were analysed. RESULTS: There was a decrease in the number of major amputations from 34 during the first period to 13 in the second, while the number of bypasses to the infrapopliteal arteries increased from four in the first period to 21 in the second. CONCLUSIONS: An increase in the incidence of bypasses to the infrapopliteal arteries was matched by a decrease in the number of major amputations. Factors that may have contributed to the increase in the incidence of distal bypass and the decrease in the number of amputations include the availability of digital subtraction angiography, and a change in referral patterns within the hospital so that, except for trauma, all patients who were considered to be candidates for major amputation were assessed by a vascular surgeon.

Aged↗

PubMed1998

Predicting hemodialysis access failure with color flow Doppler ultrasound.

Color flow doppler ultrasound examination of the hemodialysis access was conducted in 2,792 hemodialysis patients to evaluate its value in predicting hemodialysis access failure. After baseline assessment of vascular access function with clinical and laboratory tests including color flow doppler evaluation these patients were followed for a minimal of 6 months or until graft failure occurred (defined as surgery or angioplasty intervention, or graft loss). The patient demographics and vascular accesses were typical of a standard hemodialysis patient population. On the day of the color flow doppler examination systolic and diastolic blood pressure, hematocrit, urea reduction ratio, dialysis blood flow, venous line pressure at a dialysis blood flow of 250 ml/min, and access recirculation rate were measured. At the conclusion of the study 23.5% of the patients had access failure. Case mix predictors for access failure were determined using the Cox Model. Case mix predictors of access failure were race, non-white was higher than white (p < 0.005), younger accesses had a higher risk than older accesses (p < 0.025), accesses with prior thrombosis had a higher risk of failure (p=0.042), polytetrafluoroethylene (PTFE) grafts had a higher risk than native vein fistulae (p < 0.05), loop PTFE grafts had a higher risk than straight PTFE grafts (p < 0.025), and upper arm accesses had a higher risk than forearm accesses (p=0.033). Most significant, however, was decreased access blood flow as measured by color flow doppler (p < 0.0001). The relative risk of graft failure increased 40% when the blood flow in the graft decreased to less than 500 ml/min and the relative risk doubled when the blood flow was less than 300 ml/min. This study has shown that color flow doppler evaluation, quantifying blood flow in a prosthetic graft, can identify those grafts at risk for failure. In contrast, color doppler volume flow in native AV fistulae could not predict fistula survival. This technique is noninvasive, painless, portable, and reproducible. We believe that preemptory repair of an anatomical abnormality in vascular access grafts with decreased blood flow may decrease patient inconvenience, associated morbidity, and associated costs.

Arteriovenous Shunt, Surgical↗

PubMed1998

Pitfalls in placebo-controlled trials in palliative care: dexamethasone for the palliation of malignant bowel obstruction.

To determine the effect of dexamethasone when treating malignant bowel obstruction, 35 patients were randomized to receive intravenous dexamethasone or a placebo, crossing over to the alternate treatment arm if there had been no resolution of obstruction by day 5. This was done in two consecutive studies. Patients were stratified according to whether or not they had received specific anticancer therapy within 28 days of study. In trial 1, 15 out of 22 patients 'responded' (resolution of obstruction by day 5; 10 on dexamethasone, five on placebo). Eleven out of 15 patients were 'on treatment'. In trial 2, six out of 13 responded (three on dexamethasone, three on placebo); three out of six were 'on treatment'. When both studies are combined, 60% (21/35) patients responded (13 on dexamethasone, eight on placebo). Poor patient accrual terminated both studies. Numbers are too small to allow a combination of studies or formal statistical analysis. We are unable to make any conclusion as to the effectiveness of dexamethasone in the palliation of malignant bowel disease.

Adult↗

PubMed1998

The use of the Edmonton Symptom Assessment Scale (ESAS) within a palliative care unit in the UK.

The Edmonton Symptom Assessment scale (ESAS) was used on 1004 occasions to assess 71 patients with advanced malignant disease admitted to a palliative care unit in the UK over a six-week period. The median length of inpatient stay was eight days (range 1-36) and the median survival from start of ESAS to death was 16 days (range 2-202). Across all patients there was a trend towards worsening symptom scores over the first five days from admission with a significant deterioration in appetite scores. When scores were analysed retrospectively over five days according to outcome (death--group 1, or discharge--group 2) there was a significant improvement in pain scores in group 2 but no change in overall score, and a significant deterioration in activity, drowsiness and appetite in group 1 with no change in overall score. ESAS did not seem an appropriate tool in this group of patients as the total symptom scores were so often biased by the inevitable increase in individual symptom scores immediately prior to death.

Adult↗

PubMed1997

ABO blood group incompatibility in liver transplantation: a single-centre experience.

BACKGROUND: For most organ transplantation (Tx), ABO blood group incompatibility (ABOI) is an absolute contraindication because of the high incidence of hyperacute rejection (HAR). While HAR occurs in ABOI liver Tx (LTx), it is known that some liver grafts can be accepted. METHODS: ABO-incompatible (ABOI) liver allografts were used in seven of 355 orthotopic LTx operations performed at our institution over a 10-year period. All seven recipients were in fulminant hepatic failure (FHF) prior to Tx. RESULTS: Following Tx, all grafts functioned immediately. One patient died without recovering consciousness. Six patients recovered consciousness following Tx but three patients subsequently required re-transplantation (with ABO-compatible grafts (ABOC)) because of severe acute rejection (2) and chronic rejection (1). Hyper-acute rejection did not occur. All six patients are now well, with a mean survival of 61.5 months. When compared to 36 other FHF patients who received ABOC grafts, graft survivals were 3/7 (43%) for ABOI versus 23/36 (64%) for ABOC (P = not significant (NS)). Patient survivals were 6/7 (85.7%) for ABOI patients and 23/36 (64%) for ABOC (P = NS). The re-transplantation rate was significantly higher in the ABOI group (P = 0.001). CONCLUSIONS: The results confirm that ABOI liver grafts should be used in urgent circumstances when compatible grafts are not available. Some grafts function indefinitely, while those that fail may function for sufficient time to allow successful retransplantation with ABOC grafts.

ABO Blood-Group System↗