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A Lees

Publications and source records attributed to A Lees.

At least 91 records · Page 5Linked to original sources
PubMed1995

Olfactory function in atypical parkinsonian syndromes.

INTRODUCTION: Olfaction is markedly impaired in patients with idiopathic Parkinson's disease (IPD). This deficit contrasts with reports of preserved or only mildly reduced olfaction in patients with atypical parkinsonism. However, the sensitivity and specificity of olfactory function testing in the differential diagnosis of parkinsonian syndromes has not been studied. In addition, olfactory function in patients with corticobasal degeneration (CBD) is unknown. MATERIAL AND METHODS: Using the University of Pennsylvania Smell Identification Test (UPSIT) with a test score ranging from 0 to 40 we studied olfactory function in patients with IPD as well as other parkinsonian syndromes including CBD and progressive supranuclear palsy (PSP). RESULTS: UPSIT scores in 118 patients with IPD, 29 with MSA, 15 with PSP, and 7 patients with CBD, as well as in 123 healthy control subjects revealed a marked impairment in the IPD group in contrast to mild impairment in MSA patients and normal olfaction in PSP and CBD patients. An UPSIT score of 25/40 was associated with a sensitivity of 77% and a specificity of 85% in differentiating IPD from atypical parkinsonism. CONCLUSIONS: These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Adult↗
PubMed1995

T cell-independent antigens type 2.

In this review we have attempted to define the characteristics of TI-2 antigens that enable them to stimulate antibody production in the absence of T cell help. One of the most critical properties of this group of antigens is their ability to deliver prolonged and persistent signaling to the B cell. This by itself is not however sufficient to stimulate Ig synthesis, and they must therefore stimulate non-T cells to interact with the B cells either directly or indirectly via cytokine production. There is evidence implicating the NK cell and T cell as playing this important role in response to TI antigens. Furthermore, we discuss the importance of cytokines such as IL-3, GMCSF, and IFN-gamma, which significantly enhance antibody production by these antigens. Finally, we present evidence demonstrating that B cell activation via TI stimuli does not play merely a permissive role in allowing for cell cycle entry and enhanced responsiveness to other stimuli. Rather, the nature of the B cell activating signal is critical in determining the quantitative and qualitative profile of Ig isotype production.

Animals↗
PubMed1995

A biomechanical comparison of the SACH, Seattle and Jaipur feet using ground reaction forces.

The Jaipur prosthetic foot was developed in India in response to specific socio-cultural needs of Indian amputees. It is being used extensively in India and several other developing countries. Its claim of being a cheaper and satisfactory alternative to other prosthetic feet has not been investigated biomechanically. The present study was undertaken to compare its biomechanical properties with the SACH and Seattle feet, using ground reaction forces. Three trans-tibial amputees participated in the experiment which measured the ground reaction force data using a Kistler force plate. Subject's normal foot was used as a reference. Six variables from the vertical and anteroposterior components of ground reaction forces were quantified, their statistical analysis showed that the normal foot generates significantly larger ground reaction forces than the prosthetic foot. The shock absorption capacity of the SACH foot was found to be better when compared with the other two feet, while the Jaipur foot allowed a more natural gait and was closer in performance to the normal foot. None of the prostheses significantly influenced the locomotor style of the amputees.

Adult↗
PubMed1994

Antigen presentation is enhanced by targeting antigen to the Fc epsilon RII by antigen-anti-Fc epsilon RII conjugates.

Targeting Ag to the Fc epsilon RII by Ag-specific IgE has been shown to be an efficient means of enhancing Ag presentation by B cells to Ag-specific T cells. To take advantage of the Fc epsilon RII as a targeting molecule and to investigate whether IgE was required for mediation of the enhanced stimulation, Ag was covalently coupled to anti-Fc epsilon RII by using heterobifunctional crosslinking reagents. These Ag-Ab conjugates were used with T cell lines specific for the Ags, OVA (BB6.5) or rabbit gamma-globulin (CDC35 and D1.6), and splenic B cells to examine both B cell and T cell proliferation in vitro. Significant presentation of Ag-anti-Fc epsilon RII conjugates was apparent at doses of Ag 1,000- to 10,000-fold lower than seen with unconjugated Ag alone. Ag presentation with the use of anti-Fc epsilon RII-Ag conjugates was as good as or better than conjugates with Ab to the adhesion molecule Pgp-1 or control Ab in T cell proliferation and better than those conjugates in B cell proliferation assays (10- to 100-fold). Anti-Fc epsilon RII-Ag conjugates were clearly more effectively presented than Ag-anti-Fc gamma RII conjugates (> 100-fold). Mouse Fc epsilon RII is presently known to be expressed on B cells and follicular dendritic cells and these in vitro results suggest that the conjugates would be useful tools for investigating the role of IgE-mediated B cell Ag presentation in vivo. BALB/c mice immunized with OVA-anti-Fc epsilon RII conjugates made a quite significant OVA-specific IgG1 response and a detectable IgE response. No detectable Ab was produced in response to OVA alone and a minimal response was seen when an isotype-matched control conjugate was used. Thus, the results indicate that Fc epsilon RII targeting is operative both in vivo and in vitro.

Animals↗
PubMed1994

Induction of B cell and T cell tolerance in vivo by anti-CD23 mAb.

T cell tolerance can be induced by B cell presentation of Ags to naive T cells. To further characterize this mechanism of T cell tolerance induction, we have investigated the effects of injecting mice with an intact rat IgG2a Ab, which binds to the B cell low-affinity Fc epsilon receptor (CD23), on the responsiveness of B cells and T cells to rat IgG2a. Our observations indicate that 1) intravenous, subcutaneous, or intraperitoneal injection of this Ab induces antigen-specific B cell and T cell tolerance; 2) both forms of tolerance are induced more completely by injection of rat IgG2a anti-CD23 mAb than by injection of an equal dose of a control rat IgG2a Ig; and 3) reduced responsiveness to Ag is seen as early as 1 to 3 days after anti-CD23 mAb injection and reaches maximum levels by 7 days after injection. Although tolerance induced by the injection of soluble proteins has been reported to be characterized by reduced production of IL-2 and IFN-gamma, but normal production of IL-4, injection of mice with rat IgG2a anti-mouse CD23 mAb greatly decreases the IL-4 response to a rat IgG2a immunogen that normally induces a large IL-4 response.

Animals↗
PubMed1994

In vivo activation of naive T cells by antigen-presenting B cells.

In vivo experiments were performed to determine if the cross-linking of mlg on antigen-presenting B cells could induce them to present Ag to naive T cells in a stimulatory rather than a tolerogenic fashion. Mice were injected with a foreign mAb to a B cell Ag (Fc epsilon RII or CR1), and/or a self-anti-IgD mAb. Injection of either mAb alone failed to induce an Ab response; however, simultaneous injection of the foreign anti-B cell mAb plus the self-anti-IgD mAb stimulated a large response. Inasmuch as injection of the anti-IgD mAb should not have facilitated transfer of the foreign mAb to dendritic cells, this observation suggests that cross-linking of B cell mlg can induce B cells to acquire the ability to present Ag to naive T cells in an activating manner. Furthermore, when injected with anti-IgD mAb, both foreign anti-B cell mAbs were more potent in inducing Ab responses in this system than were isotype-matched control mAbs, consistent with the hypothesis that T cells were activated by Ag-presenting B cells. Results of dose-response and cell transfer studies, however, suggested that stringent cross-linking of B cell mlg on large numbers of B cells is required for B cell Ag presentation to induce T cell activation rather than tolerance. Therefore, these observations suggest that professional APCs usually are required to activate naive T cells, and that B cell Ag presentation can only activate naive T cells under unusual circumstances.

Animals↗
PubMed1994

Enhanced immunogenicity of protein-dextran conjugates: I. Rapid stimulation of enhanced antibody responses to poorly immunogenic molecules.

In view of our observation that anti-immunoglobulin antibody conjugated to high-molecular-weight dextran stimulates high levels of B-cell activation (Brunswick et al. J. Immunol. 1989, 143, 1239), we coupled T cell-dependent antigens to dextran. When mice were immunized, in the absence of adjuvant, with a BSA-dextran conjugate (BSA-dex), a persistent, high-titre anti-BSA IgG1 response was induced. Titres were dose-dependent and seen with as little as 10 micrograms of conjugated protein. Anti-BSA titres were detected as early as day 7, usually peaked at about day 14 and persisted for at least 4 weeks. Anti-hapten antibodies were also elicited in mice that were immunized with haptenated BSA covalently bound to dextran, and secondary responses could be induced even after inoculation of the unconjugated protein. Covalent attachment of the protein to the polymer was necessary, and the response was specific, as coinjection of BSA-dex and an unrelated antigen, goat IgG, did not elicit detectable anti-goat antibodies. The immunogenic potential of these conjugates did not depend on the ability of the dextran carrier to induce antibody, inasmuch as they stimulated high levels of anti-protein antibody in mice unresponsive to dextran. A minimum size dextran polymer was required for enhanced immunogenicity as conjugates of BSA with dextran of molecular mass 500 or 2000 kDa but not of 70 kDa gave detectable anti-BSA titres.

Adjuvants, Immunologic↗
PubMed1994

The relation between isometric lifting strength and muscular fitness measures.

The purpose of this study was to construct an isometric lift dynamometer and relate isometric lifting strength to dynamic measures of muscular fitness, leg and back strength and muscular power output. Thirty-one male subjects, aged 19-24 years, performed a standing broad jump (for distance), a vertical jump (for flight time), 3 maximal pulls (for peak power) on a rowing ergometer and maximal isometric leg and back extensions on a conventional dynamometer. The results of these tests were correlated with the maximum isometric lifting strength (MILS) obtained on the lift dynamometer using cluster correlation and multiple regression. Significant correlations (p < 0.001) were found between isometric lifting strength and back strength (BS) (r = 0.59), and leg strength (LS) (r = 0.74). A significant correlation was also noted between isometric lifting strength and both standing broad jump (SBJ) (r = 0.58, p < 0.001) and power output (PO) (r = 0.38, (p < 0.05). Multiple regression analysis was used to predict lifting performance from a battery of standard fitness tests. The prediction equation for maximal isometric lifting strength included the terms LS, BS, SBJ and PO (r = 0.80). The relation between isometric lifting strength and other muscular fitness variables suggest that the method used provides an acceptable measure of strength and an indication of the involvement of back and leg musculature in squat lifting.

Adult↗
PubMed1994

Spinal shrinkage in unloaded and loaded drop-jumping.

Plyometric activities, engaging the muscle in a stretch-shortening cycle, are widely used in athletic training. One such plyometric exercise is drop-jumping, where the athlete drops from a raised platform and immediately on landing performs a maximal vertical jump. These actions are also performed with the athlete externally loaded by the addition of weights to provide greater resistance. Exercises which involve repeated impacts have been shown to give rise to a loss of stature (shrinkage) which can be measured by means of a sensitive stadiometer. This study examined the shrinkage induced by unloaded and loaded drop-jumping from a height of 26 cm. Eight male subjects, aged 20-24 years, performed the test protocol three times, at the same time of day on each occasion. Fifty drop-jumps from a height of 26 cm were performed with no additional load and with a load of 8.5 kg carried in a weighted vest. The third condition was a standing trial where the subject stood for 10 min (the time taken to perform the jumps) wearing the weighted vest. Stature was measured before exercise, immediately after exercise and after a 20 min standing recovery. On a separate occasion the regimen was performed and the vertical reaction force was measured using a Kistler force platform. The mean change in stature for the two jump conditions showed shrinkages of 0.62 (+/- 0.43) mm for unloaded and 2.14 (+/- 1.56) mm for the loaded (p < 0.05). The variance in shrinkage was greater in the loaded case compared to the unloaded condition (p < 0.05) indicating a wider range of jumping strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Optimal drop heights for plyometric training.

The purpose of this study was to investigate the effects of drop height in the performance of plyometric training. Thirty male subjects were asked to perform drop jumps from heights of 0.12, 0.24, 0.36, 0.46, 0.58, and 0.68 m, as well as counter-movement jumps and squat jumps. They performed their jumps on a Kistler force platform, and the resultant force trace was integrated to calculate negative displacement of the total body centre of gravity (CG), net height rise of the CG, maximum vertical force, maximum vertical velocity, and peak instantaneous power output derived from the product of force and velocity. The results showed that the best performance in all measured parameters was for the drop height of 0.12 m. This finding differed from results of similar studies reported in the literature by others (Asmussen and Bonde-Petersen 1974, Bosco and Komi 1978). This finding was interpreted in terms of a skill and co-ordination element in the performance of plyometric movements, in contrast to a natural biomechanical response to imposed load, and the state of muscle training and competency.

Adult↗
PubMed1994

The longitudinal variability of ground reaction forces in experienced and inexperienced runners.

The hypothesis of a 'movement pattern fixation' or 'movement stereotype' for running was tested by measuring four ground reaction force variables on three separate test sessions in a longitudinal study. Of the four variables chosen to investigate this hypothesis, two reflected the shock absorption characteristics of a runner plus footwear and two reflected characteristics of running style. The former two were the magnitude of the vertical force impact peak, and the force load rate leading to this peak, while the latter two were the impulses of the breaking and propulsion phases of foot contact obtained from the anterior-posterior component of the ground reaction force. Two groups of subjects were used, seven experienced runners and seven inexperienced runners. The results showed evidence of a 'movement pattern fixation' in seven of the fourteen subjects. Thirteen subjects showed substantial differences (p < 0.001) in one or more variable, while only one subject did not show any difference in any variable across all test sessions. Differences between experienced and inexperienced runners were small for the shock absorption variables, but marked for the running style variables. Generally inexperienced runners demonstrated greater braking and propulsion impulses, and greater variability in these two variables, indicating that they were using a less economical action. It is concluded that a movement pattern fixation was shown to exist, and has implications for the testing of sports equipment. These implications are to do with the conditions required to establish the efficacy of sports equipment through athlete response testing.

Adult↗
PubMed1993

Direct detection of major histocompatibility complex class I binding to antigenic peptides using surface plasmon resonance. Peptide immobilization and characterization of binding specificity.

We have developed model systems in which the binding of purified, genetically engineered, soluble analogues of major histocompatibility complex (MHC) class I molecules to immobilized antigenic peptides can be monitored in real time using surface plasmon resonance (SPR). Synthetic analogues of several peptides known to bind different mouse and human MHC class I molecules were prepared with cysteine residues substituted at appropriate positions. The analogue peptides were immobilized via the bifunctional reagent N-gamma-maleimidobutyryloxy-succinimide to amino groups generated on the dextran-modified gold surface of a biosensor flow cell. Using this approach, each position in the sequence of an H-2Ld-specific viral peptide, pMCMV (YPHFMPTNL), was used for coupling, and the resulting surfaces were tested for binding of the soluble analogue of H-2Ld, H-2Lds. In accord with our previously described H-2Ld/pMCMV three-dimensional structural model, only those residues of the peptide that remain exposed following binding (positions 4-8) can be replaced by cysteine and used for coupling. Stable binding of soluble MHC class I molecules, H-2Lds, H-2Dds, H-2Kbs, and HLA-A2s to their respective immobilized cognate peptides was detected by SPR. Specificity of the peptide/MHC interaction was characterized both by direct binding using immobilized peptides and by competition with peptides in solution, and in general was consistent with known immunological reactivity. Some peptides bound not only their cognate MHC molecule, but others at lower apparent affinity. Measurement of real time binding of MHC class I molecules to peptides immobilized through specific side chains suggests the application of a similar approach to the study of the interaction of peptides with a wide variety of peptide-binding macromolecules.

Alleles↗
PubMed1993

Persistent calcium elevation correlates with the induction of surface immunoglobulin-mediated B cell DNA synthesis.

Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ([Ca2+]i). These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low-level but persistent sustained or cyclic elevations in [Ca2+]i. In marked contrast, early and nonsustained elevations in [Ca2+]i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran-anti-Ig conjugate which induced very high levels of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in [Ca2+]i as detected by flow cytometry. Finally, B cells from X-linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in [Ca2+]i, but do not show persistent calcium elevations. These data suggest that the rapid and large increases of [Ca2+]i seen in lymphocytes within seconds after antigen receptor ligation may be associated with entry in G1, whereas low-level but persistent elevations may be the hallmark of a cell destined to synthesize DNA.

Animals↗
PubMed1993

IL-10 inhibits T cell-independent but not T cell-dependent responses in vitro.

Lymphokines play a key role in T cell-independent (TI) Ag-induced responses. We recently showed that IL-10 potently inhibits Ig production stimulated by TI-2 Ag + IL-5. In view of our recent findings that the B cell activator can determine the effect lymphokines will have on Ig production and on isotype selection, we analyzed the effect of IL-10 on Ig production induced by other TI antigens and T cell-dependent Ag. These data demonstrate that IL-10 inhibited IL-5-induced Ig production stimulated by TI-1 and by TI-2 Ag, but had no effect on an in vitro T cell-dependent Ag-specific anti-SRBC-induced response or on a T cell-induced polyclonal response mediated by anti-CD3-activated T cell clones. IL-10 inhibited IgM, IgG1, IgG2a, and IgG3 secretion by B cells costimulated by LPS or anti-delta-dextran. IL-10 did not interfere with induction of class II MHC Ag expression or cell enlargement that was stimulated by LPS or anti-delta-dextran and had no detrimental effect on cell viability. IL-4 reversed the IL-10-mediated inhibition of IgG1 and IgM secretion stimulated by anti-delta-dextran or LPS-activated cells in the presence of IL-5. A 72 h, but not 24 h, exposure to IL-4 at initiation of culture with anti-delta-dextran + IL-5 + IL-10 was necessary to reverse the IL-10-mediated inhibition of IgM secretion. Our data suggest that IL-10 can selectively inhibit TI Ag-induced responses when other T cell-derived stimulatory lymphokines are not present and further emphasize the specific role of the B cell activator in influencing the responsiveness of B cells to lymphokines.

Animals↗
PubMed1993

Comparative in vitro analysis of proliferation, Ig secretion, and Ig class switching by murine marginal zone and follicular B cells.

We have previously demonstrated that activation of murine B cells by dextran-conjugated anti-IgD antibodies may serve as a polyclonal, in vitro model system for studying immune responses to T cell-independent type 2 (TI-2) Ag, as exemplified by the bacterial polysaccharides. Because in vivo Ig responses to TI-2 Ag are mediated primarily by B cells resident in the splenic marginal zone, we wished to determine whether this reflected an intrinsic difference in the responsiveness of marginal zone B cells (MZB) compared with follicular B cells (FB) to this class of Ag. In this report we demonstrate that highly purified MZB, isolated by electronic cell sorting, exhibit a lower proliferative response in vitro in response to unconjugated anti-Ig antibody as well as to dextran- or Sepharose-conjugated anti-IgM or anti-IgD antibodies, whereas they proliferate equal to or better than FB when stimulated by other B cell mitogens including LPS, Salmonella typhimurium mitogen, or anti-CD3-activated CD4+ Th2 cell clone. Despite the different proliferative responses of MZB and FB induced by anti-Ig, Ag receptor cross-linkage stimulates comparable increases in intracellular free calcium concentrations in both of these B cell populations. Furthermore, MZB secrete Ig and undergo Ig isotype switching to a comparable degree, relative to FB, in response to both T cell-dependent and T cell-independent stimuli. This suggests that the compartmentalization of TI-2 responses to the splenic marginal zone rather than the follicular zone reflects something other than the intrinsic responsiveness of the B cells from these two sites.

Animals↗
PubMed1993

Dextran-conjugated anti-IgD antibodies inhibit T cell-mediated IgE production but augment the synthesis of IgM and IgG.

We previously demonstrated that anti-IgD antibodies conjugated to dextran (alpha delta-dex) were a potent co-stimulus for Ig secretion by resting murine B cells in the presence of cytokines. However, although alpha delta-dex stimulated the secretion of most Ig isotypes it selectively failed to costimulate IgE production even in the presence of high concentrations of IL-4. Earlier reports indicated that unconjugated anti-IgM, which was not an effective costimulus for Ig secretion, in fact inhibited Ig production induced by LPS. We determined the effect of alpha delta-dex, at concentrations that costimulated cytokine-induced Ig secretion, on Ig production by LPS- or T cell-activated B cells, and whether IgE production was affected in a selective manner. We observed that alpha delta-dex inhibited Ig isotype production (IgE > IgG > IgM) by LPS-activated B cells, while further stimulating their proliferation. This effect of alpha delta-dex was mediated directly at the level of the B cell and was accompanied by a comparable inhibition in Ig class switching, as assessed by flow cytometric analysis of membrane Ig isotype-positive cells. The inhibitory effects of alpha delta-dex on LPS-induced Ig secretion and class switching occurred at 1000-fold lower concentrations of anti-IgD than that reported necessary for inhibition by unconjugated anti-IgM. Whereas IL-4 + IL-5 costimulated Ig isotype production by alpha delta-dex-activated cells, the further addition of LPS led to a marked ablation of the Ig secretory response indicating the cross-inhibitory effects of these two modes of B cell activation. By contrast, alpha delta-dex augmented IgM and IgG1 secretion by resting B cells stimulated with either an anti-CD3-activated CD4+ Th2 clone or with activated T cell membranes in combination with IL-4 + IL-5. However, alpha delta-dex potently inhibited T cell-mediated IgE secretion. These findings underscore the existence of, and demonstrate a number of novel interrelationships between, three distinct pathways of B cell differentiation induced by different modes of activation. Further, the observation that pg/ml quantities of alpha delta-dex selectively inhibits T cell-induced IgE production in vitro suggests a novel strategy to down-regulate this Ig isotype in vivo.

Adjuvants, Immunologic↗
PubMed1993

A biomechanical analysis of the last stride, touch-down and take-off characteristics of the women's long jump.

This study was concerned with the measurement of a selection of performance variables from competitors in the women's long jump final of the World Student Games held in Sheffield, UK in July 1991. Several performances of each of six finalists were recorded on cine-film at 100 Hz. Resulting planar kinematic data were obtained for the last stride, touch-down and take-off. For the analysis, the point of maximum knee flexion was established and this was used to represent the point at which the compression phase had ended. A variety of variables describing the position, velocity and angular changes are presented as descriptive data. In addition, these were used to compute energies on the basis of a whole body model. The data were interpreted on the basis of a technique model of long jumping established from the literature. It was confirmed that take-off velocity was a function of touch-down velocity, and that there was an increase in vertical velocity at the expense of a reduction of horizontal velocity. An attempt was made to identify the mechanisms acting during the touch-down to take-off phase which were responsible for generating vertical velocity. It was concluded that there was evidence for mechanical, biomechanical and muscular mechanisms. The former relates to the generation of vertical velocity by the body riding over the base of support; the second is the elastic re-utilization of energy; and the third is the contribution by concentric muscular contraction.

Biomechanical Phenomena↗