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Biomedical subjects

J Biggs

Publications and source records attributed to J Biggs.

At least 19 recordsLinked to original sources
PubMed2001

Regional mapping of low-affinity kainate receptors in mouse brain using [(3)H](2S,4R)-4-methylglutamate autoradiography.

Recent data indicate that (2S,4R)-4-methylglutamate is a selective agonist for low affinity (GluR5 and GluR6) kainate receptor subunits. In the present study, we have employed [(3)H](2S,4R)-4-methylglutamate to examine low affinity kainate receptor distribution in mouse brain. [(3)H](2S,4R)-4-Methylglutamate labelled a single site in murine cerebrocortical membranes (K(d)=9.9+/-2.7 nM, B(max)=296.3+/-27.1 fmol mg protein(-1)). The binding of 8 nM [(3)H](2S,4R)-4-methylglutamate was displaced by several non-NMDA receptor ligands (K(i)+/-S.E.M.): domoate (1.1+/-0.2 nM)>kainate (7.1+/-1.1 nM) >> L-glutamate (187.6+/-31.9 nM) >> (S)-alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) (>50 microM). [(3)H](2S,4R)-4-Methylglutamate autoradiography revealed a widespread regional distribution of low affinity kainate receptors. Highest binding densities occurred within deep layers of the cerebral cortex, olfactory bulb, basolateral amygdala and hippocampal CA3 subregion. Moderate labelling was also evident in the nucleus accumbens, dentate gyrus, caudate putamen, hypothalamus and cerebellar granule cell layer. These data show that [(3)H](2S,4R)-4-methylglutamate is a useful radioligand for selectively labelling low affinity kainate receptors.

Animals↗
PubMed2001

Electrical resistivity of the upper arm and leg yields good estimates of whole body fat.

Single frequency bioelectrical impedance analysis is an inexpensive, quick and painless means of estimating body composition. However, current approaches to estimating body composition from segment resistivity have some drawbacks. The purpose of this study was to overcome these limitations by developing a better model of the relationship between resistivity and body composition. A three-compartment model of body mass and body segment resistivity is presented and calibrated to predict %Fat estimated by underwater weighing. The subject population from which the data were obtained was heterogeneous. Both sexes were represented, as were a range of ages (21-44 years), ethnic backgrounds, body masses (47.0-129.0 kg) and body compositions (%Fat = 8.7-50.7%). Based on resistivity measurements from the upper arm and upper leg, and measurements of subject height and weight, the model predicted %Fat with errors comparable to those reported for other methods based on segmental resistivity. All the terms in the calibrated model represented a physical component of the body and show reasonable agreement with resistivity measured in tissue samples. In short, predicting %Fat from resistivity of the proximal arm and leg segments compares favourably with other methods based on segment resistivity.

Adipose Tissue↗
PubMed2001

The revised two-factor Study Process Questionnaire: R-SPQ-2F.

AIM: To produce a revised two-factor version of the Study Process Questionnaire (R-SPQ-2F) suitable for use by teachers in evaluating the learning approaches of their students. The revised instrument assesses deep and surface approaches only, using fewer items. METHOD: A set of 43 items was drawn up for the initial tests. These were derived from: the original version of the SPQ, modified items from the SPQ, and new items. A process of testing and refinement eventuated in deep and surface motive and strategy scales each with 5 items, 10 items per approach score. The final version was tested using reliability procedures and confirmatory factor analysis. SAMPLE: The sample for the testing and refinement process consisted of 229 students from the health sciences faculty of a university in Hong Kong. A fresh sample of 495 undergraduate students from a variety of departments of the same university was used for the test of the final version. RESULTS: The final version of the questionnaire had acceptable Cronbach alpha values for scale reliability. Confirmatory factor analysis indicated a good fit to the intended two-factor structure. Both deep and surface approach scales had well identified motive and strategy subscales. CONCLUSION: The revision process has resulted in a simple questionnaire which teachers can use to evaluate their own teaching and the learning approaches of their students.

Factor Analysis, Statistical↗
PubMed2001

Peripheral blood stem cell transplantation for rheumatoid arthritis--Australian experience.

Trials of high dose immunosuppression and peripheral blood stem cell transplantation (PBSCT) in patients with severe rheumatoid arthritis (RA) have now commenced based on encouraging data from case reports of patients with coexistent malignancy and animal transplant models. Early case reports in Australia documented the potential for cure of RA in most patients receiving allogeneic or syngeneic transplants. However, the relatively high morbidity and mortality of these procedures has necessitated the use of autologous PBSCT. in accordance with international guidelines released by the EBMT/EULAR working party. Phase I trials in autologous PBSCT have seen substantial remissions of RA in the majority of patients who had previously failed all available therapies. Recurrence of disease occurs in most patients usually within 2 years; however, the use of disease modifying agents after recurrence results in substantial amelioration of the disease, again suggesting a form of "immunomodulation." This observation raises the possibility of maintenance therapy associated with procedure to prolong responses. Other modifications of the procedure are discussed, including T cell depletion of the graft, currently the subject of a randomized trial.

Antigens, CD34↗
PubMed2000

Both service and training demand attention in obstetrics and gynaecology.

New proposals for workforce planning, training and ways of working in the NHS are under consideration. Aspects of service, training and workforce in obstetrics and gynaecology that call out for change include training in the senior house officer grade, especially for GPs and non-EC doctors, and the work of consultants. Proposals for change present a golden opportunity for the specialty to lead in new systems of both service and training, which are closely linked.

Delivery of Health Care↗
PubMed2000

Self-tolerance and the composition of T cell repertoire.

T cell recognition of self-major histocompatibility complex-peptide complexes dictates the composition of the T cell receptor repertoire. Research projects in our laboratory deal with the mechanisms that regulate the composition of the repertoire specific for self-antigens and the defects that can result in autoimmunity. Two different types of disease models are under investigation: juvenile (type I) diabetes and cancer. Both of these diseases are impacted by the presence of anti-self CD8 cells, yet in opposite ways. By understanding the mechanisms of peripheral tolerance and the reasons they fail in autoimmunity, we may learn how to prevent undesirable autoimmunity and how to encourage an autoimmune response when it is needed to eliminate tumor cells.

Autoimmunity↗
PubMed1999

A patient decision aid regarding antithrombotic therapy for stroke prevention in atrial fibrillation: a randomized controlled trial.

CONTEXT: Decision aids are tools designed to help patients participate in the clinical decision-making process. OBJECTIVE: To determine whether use of an audiobooklet (AB) decision aid explaining the results of a clinical trial affected the decision-making process of study participants. DESIGN: Randomized controlled trial conducted from May 1997 to April 1998. SETTING: Fourteen centers that participated in the Stroke Prevention in Atrial Fibrillation (SPAF) III trial. PARTICIPANTS: A total of 287 patients from the SPAF III aspirin cohort study, in which patients with atrial fibrillation and a relatively low risk of stroke received 325 mg/d of aspirin and were followed up for a mean of 2 years. INTERVENTION: At the end of SPAF III, participants were randomized to be informed of the study results with usual care plus use of an AB (AB group) vs usual care alone (control group). The AB included pertinent information to help patients decide whether to continue taking aspirin or switch to warfarin. MAIN OUTCOME MEASURES: Patients' ability to make choices regarding antithrombotic therapy, and 6-month adherence to these decisions. Their knowledge, expectations, decisional conflict (the amount of uncertainty about the course of action to take), and satisfaction with the decision-making process were also measured. RESULTS: More patients in the AB group made a choice about antithrombotic therapy than in the control group (99% vs 94%; P = .02). Patients in the AB group were more knowledgeable and had more realistic expectations about the risk of stroke and hemorrhage (in the AB group, 53%-80% correctly estimated different risks; in the control group, 16%-28% gave correct estimates). Decisional conflict and satisfaction were similar for the 2 groups. After 6 months, a similar percentage of patients were still taking their initial choice of antithrombotic therapy (95% vs 93%; P = .44). CONCLUSIONS: For patients with atrial fibrillation who had participated in a major clinical trial, the use of an AB decision aid improved their understanding of the benefits and risks associated with different treatment options and helped them make definitive choices about which therapy to take. Further studies are necessary to evaluate the acceptability and impact of decision aids in other clinical settings.

Aged↗
PubMed1999

Autologous versus allogeneic transfusion: patients' perceptions and experiences.

BACKGROUND: Preoperative autologous donation is one way to decrease a patient's exposure to allogeneic blood transfusion. This study was designed to determine patients' perceptions about the autologous blood donation process and their experiences with transfusion. METHODS: To assess patient perception, a questionnaire was administered a few days before surgery to patients undergoing elective cardiac and orthopedic surgery in a Canadian teaching hospital. All patients attending the preoperative autologous donation clinic during a 10-month period were eligible. A convenience sample of patients undergoing the same types of surgery who had not predonated blood were selected from preadmission clinics. Patient charts were reviewed retrospectively to assess actual transfusion practice in all cases. RESULTS: A total of 80 patients underwent cardiac surgery (40 autologous donors, 40 nondonors) and 73 underwent orthopedic surgery (38 autologous donors, 35 nondonors). Of the autologous donors, 75 (96%) attended all scheduled donation appointments, 73 (93%) said that they were "very likely" or "likely" to predonate again, and 75 (96%) said that they would recommend autologous donation to others. There was little difference in preoperative symptoms between the autologous donors and the nondonors, although the former were more likely than the latter to report that their overall health had remained the same during the month before surgery (30 [75%] v. 21 [52%] for the cardiac surgery patients and 30 [79%] v. 18 [51%] for the orthopedic surgery patients). When the autologous donors were asked what they felt their chances would have been of receiving at least one allogeneic blood transfusion had they not predonated, the median response was 80%. When they were asked what their chances were after predonating their own blood, the median response was 0%. The autologous donors were significantly less likely to receive allogeneic blood transfusions (6 [15%] for cardiac surgery and 3 [8%] for orthopedic surgery) than were the nondonors (14 [35%] for cardiac surgery and 16 [46%] for orthopaedic surgery). They were, however, more likely to receive any transfusion (autologous or allogeneic) than were the nondonors (25 [63%] v. 14 [35%] for cardiac surgery and 31 [81%] v. 16 [46%] for orthopedic surgery). INTERPRETATION: Patients who underwent preoperative autologous blood donation were positive about the experience and did not report more symptoms than patients who did not donate blood preoperatively. Autologous donors overestimated their chances of receiving allogeneic blood transfusions had they not predonated and underestimated their chances after they had predonated. They were less likely to receive allogeneic transfusions, but more likely to receive any type of transfusion, than were patients who did not predonate.

Aged↗
PubMed1999

Extrinsic muscles of the hand signal fingertip location more precisely than they signal the angles of individual finger joints.

Studies have demonstrated that muscle spindle organs provide the majority of the proprioceptive information available to the nervous system about limb position. Other studies suggest that a sense of position may be lacking in the fingers, as subjects were unaware of rather large excursions of finger joints if the excursions were made slowly enough. We sought to investigate the basis for this unexpected finding with a biomechanical model of the human long finger and the forearm muscles which actuate it, in order to study potential contributions of spindle organs in the extrinsic muscles of the hand to a sense of position of the finger. The model, based on cadaver data, allowed us to determine how precisely estimates of the lengths of the extrinsic finger muscles can be transformed into estimates of: (1) the flexion/extension angles of the individual finger joints, and (2) the location of the fingertip in the flexion/extension plane. We found that, for some finger positions, length information from all three extrinsic muscles was not sufficient to precisely estimate the flexion angles of all finger joints. Precision of joint angle estimates could be as poor as +/- 18% of joint range of motion. However, length information from just two of the extrinsic muscles taken together could always provide information sufficient to estimate the location of the fingertip relative to the metacarpophalangeal joint within a reasonably small tolerance (+/- one-half thickness of the fingertip). Furthermore, it was possible to make this estimate without determining any of the finger joint angles. These results suggest that spindles in the extrinsic muscles alone can signal fingertip location, even though they may not provide sufficient information to estimate the individual joint angles that set the position of the fingertip. Thus, an absence of position sense for individual joints (the sense many studies have tried to measure) may say little about a sense of location of the tip of the finger.

Biomechanical Phenomena↗
PubMed1999

A three-dimensional kinematic model of the human long finger and the muscles that actuate it.

A kinematic model of the human long finger and the six muscles that actuate it is presented. The model transforms finger pose into estimates of muscle excursions and fingertip location. The effects of abduction/adduction about the metacarpo-phalangeal joint are accounted for, as are the effects of flexion of the three finger joints. A set of parameters are provided which approximate kinematics of the segments and muscles of a cadaver finger over the range of finger poses humans normally assume.

Biomechanical Phenomena↗
PubMed1999

Tumonoic acids, novel metabolites from a cyanobacterial assemblage of Lyngbya majuscula and Schizothrix calcicola.

Five new metabolites have been isolated from a lyngbyastatin 1- and dolastatin 12-producing assemblage of Lyngbya majuscula and Schizothrix calcicola collected at Tumon Bay, Guam. Structure elucidation employed 2D NMR techniques and chemical derivatization. These compounds have been assigned the trivial names tumonoic acids A (2), B (1), and C (5); methyl tumonoate A (3), and methyl tumonoate B (4). Compounds 1 and 4 were also found in a lyngbyastatin 1-producing strain of L. majuscula from Guam.

Cyanobacteria↗
PubMed1999

Biomechanical model predicts directional tuning of spindles in finger muscles facilitates precision pinch and power grasp.

Humans have a sense of static limb position derived primarily from the output of secondary muscle spindle endings. The features of finger pose these proprioceptors signal best were predicted by singular value decomposition of a kinematic model of the human long finger and the six muscles that actuate it. The analysis indicated that muscle spindles signal the location of the fingertip with less error than they signal angles of individual finger joints. The fingertip displacements for which proprioceptors have greatest sensitivity were also predicted. These fingertip displacements seem to correspond to the fine positioning of an object pinched between the fingertip and distal phalanx of the thumb. The analysis also predicted the directions in which subjects can displace the fingertip most rapidly. The directions seem to correspond to rapid closure of precision pinch or power grasp.

Biomechanical Phenomena↗
PubMed1998

The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking peptide epitope.

A high proportion of tumors arise due to mutation of the p53 tumor suppressor protein. A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues 264-272, renders cells resistant to killing by human histocompatibility leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocytes (CTLs) specific for this epitope. Acquisition of the R to H mutation at residue 273 of the human p53 protein promotes tumor growth in vivo by selective escape from recognition by p53.264-272 peptide-specific CTLs. Synthetic 27-mer p53 polypeptides covering the antigenic nonamer region 264-272 of p53 were used as proteasome substrates to investigate whether the R to H mutation at the P1' position of the COOH terminus of the epitope affects proteasome-mediated processing of the protein. Analysis of the generated products by tandem mass spectrometry and the kinetics of polypeptide processing in conjunction with CTL assays demonstrate that the R to H mutation alters proteasomal processing of the p53 protein by inhibiting proteolytic cleavage between residues 272 and 273. This prevents the release of the natural CTL epitope that spans flanking residues 264-272 as well as a putative precursor peptide. These results demonstrate that mutation of p53 not only leads to malignant transformation but may also, in some instances, affect immune surveillance and should be considered in the design of cancer vaccines.

Amino Acid Sequence↗
PubMed1998

Isolation, structure determination, and biological activity of dolastatin 12 and lyngbyastatin 1 from Lyngbya majuscula/Schizothrix calcicola cyanobacterial assemblages.

Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.

Actin Cytoskeleton↗
PubMed1998

Strategies for tumor elimination by cytotoxic T lymphocytes.

Despite differences in their tissue of origin, many tumors share high level expression of certain tumor-associated proteins. Our laboratory has focused on the possibility of utilizing antigenic components of these proteins as a focus for T-cell immunotherapy of cancer. The advantage of targeting such commonly expressed proteins is the fact that such therapy could be of value in eliminating many different types of tumors. A potential barrier in the identification of T-cell epitopes derived from these proteins and presented by tumor cells is the fact that these proteins are also expressed at low levels in some normal tissues, and therefore, self-tolerance may eliminate T cells that are capable of recognizing these epitopes with high avidity. We have utilized two different murine model systems to explore the extent to which self-tolerance may limit the immune response to a tumor-specific antigen. The first compared the ability of mice deficient in expression of murine p53 (p53 knock-out mice) and normal mice, to respond against several epitopes of the p53 protein. The second model compares the ability of conventional mice with transgenic mice that express the influenza hemagglutinin in the periphery to respond to a dominant antigenic peptide of this transgene product. In both models we have investigated the effect self-tolerance has on elimination of tumors expressing the toleragen.

Animals↗
PubMed1997

Complex regulation of CDK2 during phorbol ester-induced hematopoietic differentiation.

Phorbol myristate acetate (PMA) treatment of U937 human leukemic cells results in late G1 cell cycle arrest and terminal monocyte/macrophage-like differentiation. The PMA-induced G1 arrest involves a marked decrease in cdk2 activity, which correlates with total cdk2 dephosphorylation. Here, we show that the levels of cyclin A mRNA and protein markedly decrease during PMA-induced differentiation of U937 cells. In contrast, the level of cyclin E protein remains unchanged and in a complex with cdk2 during the entire course of PMA treatment. During the PMA-induced differentiation, cyclin E-associated cdk2 activity drops markedly. Furthermore, the amount of p27(Kip1) protein associated with cyclin E/cdk2 greatly increases 24 to 72 hours after PMA treatment. The absence of changes in p27(Kip1) mRNA levels by Northern blot suggest that the levels of this protein are controlled by posttranscriptional or posttranslational mechanism(s). These results show that the mechanisms mediating PMA-induced G1 arrest are complex. The inhibition of cdk2 activity is associated with (1) a decrease in cyclin A protein levels, (2) inactivation of cdk2 complexes, and (3) upregulation of p27(Kip1) protein.

CDC2-CDC28 Kinases↗