Showing papers by "University of Birmingham published in 1985"

Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG.

Abstract: Rheumatoid arthritis (RA) is a widely prevalent (1-3%) chronic systemic disease thought to have an autoimmune component; both humoral and cellular mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin, implying that this is both the 'antibody' (rheumatoid factor [RF]) and the 'antigen' (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (C gamma 2) domains of IgG. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of approximately 1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a 'shift' in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.

A review of Mesozoic climates

Abstract: There is overwhelming evidence, based on the distribution of distinctive sediments and fossils and oxygen isotope data, that the climate of the Mesozoic world was appreciably more equable than that of today, with no polar ice caps, but precise quantitative data are not available. Except for an episode of late Cretaceous cooling there is no good documentation of any significant change in global temperature distributions through the era. The distribution of coals and evaporites, together with other criteria, indicates a pattern of humid arid and zones appreciably different in important respects from that of today. During the Triassic and Jurassic, western Pangaea in low to middle latitudes was largely arid, but in the early Cretaceous the lands on the margin of the newly opening Central Atlantic and western Tethys experienced a humid climate. By late Cretaceous times arid zones had become very restricted in extent. Because of insufficient suitable data, attempts at climatic modelling have had only modest success, and only to a limited extent can the major long-term changes in climate between the Permian and the present be explained in terms of changing geography. The most probable explanation of Mesozoic equability is an increased atmospheric CO 2 content. A number of enigmas remain, such as the existence of flourishing forests in polar palaeolatitudes. Whereas for the late Cenozoic short-term climatic changes can be related successfully to variations in the geometry and mechanics of the earth-sun system, there is a long way to go before comparable success can be claimed for the Mesozoic.

Studies in the Byzantine Monetary Economy c.300-1450

Abstract: List of plates List of maps List of tables Abbreviations Preface and acknowledgements Introduction Part I. Economy and Society: 1. The land 2. The basic geography of settlement and society Part II. Finance: 3. The budget 4. The limiting factors Part III. Coinage (Circulation): 5. Supply 6. Supervision Part IV: Coinage (Production): 7. Administrative basis 8. History Preliminary observations, future directions Bibliographies Key to plates Indexes.

Food-conditioned eating preferences and aversions with interoceptive elements: conditioned appetites and satieties.

Abstract: The adaptive importance of acquired feeding habits has long been acknowledged in research on obesity1 and animal foraging2 for example Yet so few experiments have measured learning under physiologically and ecologically normal conditions that there is insufficient information for effective applications in the clinic and everyday life,3 the foods4 or Pharmaceuticals5 industries, or animal husbandry6 Nevertheless, it has been established that normal feeding in the laboratory rat is associatively conditioned by nutritional consequences7–11 Occasionally, aversions are conditioned However, what is usually learned is facilitation of feeding (Table 1), which accounts for much of the incentive to forage and the palatability of foods and drinks13

Falls in the healthy elderly: predisposing causes.

Abstract: One hundred healthy men and women aged 65-85 took part in a prospective study. They were clinically examined and underwent laboratory tests of gait, balance and reaction time at the start of an observation year. All falls occurring in that year were analysed in detail. Three-quarters of them were trips or slips; however, ten personal factors were identified which, if present, increased the likelihood of a fall occurring. These were: disturbance of gait following a rest period accompanied by a lighting change (in persons aged 70 and over); an absent or abnormal plantar reflex; failure to wear prescribed spectacles; the presence of anxiety/depression, of a foot problem, or of two or more self-perceived limitations on mobility; a history of former wearing of high heels; a sustained drop in pulse pressure 5 min after cessation of a rest period; restricted neck movements; and the presence of an inverse Romberg ratio. The number of circumstantial and personal factors contributing to the falls varied between thr...

A single stem cell can recolonize an embryonic thymus, producing phenotypically distinct T-cell populations

Abstract: There is much interest in early T-cell development, particularly in relation to the diversification of the T-cell receptor repertoire1,2 and the elucidation of the lineage relationships between T-cell populations in the thymus and peripheral lymphoid organs (reviewed in refs 3, 4). However, the requirements for the growth of the earliest thymic T-cell precursor in 13–14-day mouse embryo thymus in isolation from the thymic environment are unknown. Proliferation and maturation of such cells are not sustained either in the presence of monolayers of thymic stromal cells (refs. 5, 6 and see below) or by the addition of interleukin-2 (IL-2), despite the expression of receptors for this growth factor on a proportion of thymocytes displaying the immature Thy 1+ Lyt-2−L3T4− phenotype in the embryonic thymus7,8. In contrast, when maintained within the intact thymic environment in organ cultures9,10, 13–14-day thymic stem cells do show a pattern of surface marker and functional development similar to that seen in vivo, suggesting that short-range growth signals, perhaps necessitating direct contact with organized epithelial cells, are required. We have shown, by exploiting the selective toxicity of deoxyguanosine (dGuo) for early T cells, that this organ culture system can be manipulated to produce alymphoid lobes that can be recolonized from a source of precursors in a transfilter system11. We now show that recolonization of alymphoid lobes can also be achieved by association with T-cell precursors in hanging drops, allowing recolonization by exposure to defined numbers of precursors, including a single micromanipulated stem cell. Analysis of T-cell marker expression in these cultures shows that a single thymic stem cell can produce progeny of distinct phenotypes, suggesting that these marker-defined populations are not derived from separate pre-thymic precursors, but arise within the thymus.

The life-space diary: a measure of mobility in old people at home

Abstract: Thirty people aged 64 and over living at home were asked to complete a "life-space diary" for 1 month during which they were invited to attend a gait laboratory for measurements of gait and balance. Twenty-eight subjects completed the diary satisfactorily, and 24 of these also undertook the laboratory tests. The diary was acceptable and gave a good indication of the subject's mobility. There was a close correlation between mobility as derived from the diary and the laboratory measurements of gait speed and mean sway path. The diary is worthy of further evaluation as an objective record of mobility in old people at home.

Heart Rate and Oxygen Consumption during Mental Arithmetic, a Video Game, and Graded Exercise: Further Evidence of Metabolically-Exaggerated Cardiac Adjustments?

Abstract: Heart rate, plus various metabolic and ventilatory indices, were monitored while 20 young male subjects were exposed to a video game and a stressful mental arithmetic task. Measurements were also made while subjects undertook graded isotonic exercise. All measures changed as a function of psychological challenge, and during exercise physiological activity increased as an orderly function of workload. For each subject, heart rate was plotted against oxygen consumption over the various exercise loads. For the majority of subjects the analogous data points for the video game and mental arithmetic lay reliably above the exercise heart rate-oxygen consumption regression lines. When these regression lines were used to predict heart rate values during psychological challenge, the predicted values were significantly less than the values actually recorded for both tasks; although the discrepancy between predicted and actual values was on average greater with mental arithmetic, the difference was not statistically reliable. Pre-stressor baseline conditions were also associated with heart rate levels greater than predicted, albeit to a lesser extent. Finally, while both stressors produced heart rate adjustments additional to expectancies, inter-task consistency was low.

Epstein-Barr virus-positive Burkitt's lymphoma cells not recognized by virus-specific T-cell surveillance.

Abstract: The pathogenesis of Epstein–Barr (EB) virus-positive Burkitt's lymphoma (BL) appears to involve the combined actions of (1) virus-induced B-cell proliferation, and (2) a rare chromosomal translocation juxtaposing c-myc and immunoglobulin gene loci in a single B cell; holoendemic malarial infection in some way facilitates the oncogenic process1–3. Outgrowth of the EB virus-positive tumour suggests either breakdown or evasion of those immune controls, in particular cytotoxic T-cell responses against the virus-induced lymphocyte-detected membrane antigen LYDMA, which limit virus-infected B-cell numbers in healthy virus carriers4. Immunosuppression, such as that which malarial infection may induce5,6, cannot itself be a sufficient explanation in this regard since our studies have identified a number of BL patients who retain detectable LYDMA-specific T-cell surveillance7. The present work shows that in many cases of virus-associated BL, the emerging malignant clone is insensitive to such surveillance. Several EB virus-positive BL cell lines, recently established in vitro and expressing the class I histocompatibility locus antigens (HLAs) which restrict cytotoxic T-cell function, were not killed by HLA-matched LYDMA-specific effector populations in assays where the EB virus-positive lymphoblastoid cell line (LCL), derived from normal B cells of the same patient, sustained high levels of lysis.

Visual pigments and oil droplets in the penguin, Spheniscus humboldti

Abstract: The photoreceptors of the penguin,Spheniscus humboldti, were examined using a microspectrophotometer. The cones could be divided into three classes based on their visual pigment absorbance spectra [λmax 403, 450 and 543 nm (Fig. 1)], and into five classes based on their visual pigment-oil droplet combination (Fig. 4). Oil droplets were of three types (Fig. 2). The rods contained a rhodopsin with λmax at 504 nm. No double cones were observed. The penguin should be capable of good wavelength discrimination in the blue-green region of the spectrum but with poor discrimination at longer wavelengths. It is concluded that the spectral properties of the cone types indicate that the photopic vision ofS. humboldti is adapted to the spectral qualities of its aquatic environment.

On reverse engineering

Abstract: A suggested approach to the process of reverse engineering is presented from a tutorial viewpoint. Reverse engineering is considered as the process of developing a set of specifications for a complex hardware system by an orderly examination of specimens of that system. It is assumed that the specifications are being developed for the purpose of making a clone of the original hardware system, a circumstance which requires the most comprehensive form of specifications. Document formats are described for recording information and data in the reverse engineering process that are synergistic with the method recommended for use in guiding that process. The documentation suggested directs the reverse engineering process that uncovers the information which is recorded in the documents. A reverse engineering method is described that is based on the premise that a complex hardware system can be characterized as a hierarchical structure. The key feature of this method is that when it is applied to a specific level in the hardware structural hierarchy, it is used to uncover the internal particulars of a specific item of that level in terms of the elements located in the immediately subordinate level and how those elements are interconnected.

Endorphins and food intake: kappa opioid receptor agonists and hyperphagia.

Abstract: Evidence from studies which utilise either opiate receptor agonists and antagonists strongly indicate a role for endorphinergic mechanisms in the control of feeding responses. Two means by which these compounds may exert an effect on feeding can be singled-out. Firstly, emerging evidence suggests that the process of achieving satiety (terminating a meal, or choice of a commodity) may be accelerated following treatments with opiate receptor antagonists. Secondly, the preference for highly palatable solutions (sweet solutions have received most attention) in two-bottle tests is blocked after injection of opiate receptor antagonists. This finding has been interpreted in terms of the abolition of the reward or incentive quality associated with the particularly attractive flavour. These two mechanisms of action may represent two aspects of a single, fundamental process. Following an introduction to rat urination model of in vivo kappa agonist activity, the consistent effect of several kappa agonists (including the highly selective U-50,488H) to stimulate food consumption is described. Recognising that members of the dynorphin group of endogenous opioid peptides are kappa receptor ligands, some with a high degree of selectivity, and the evidence the dynorphins and neo-endorphins produce hyperphagia in rats is particularly interesting. Such lines of evidence lead to the hypothesis that peptides of the dynorphin group may act endogenously to promote the expression of normal feeding behaviour.

Distinctions between endemic and sporadic forms of epstein‐barr virus‐positive burkitt's lymphoma

Abstract: Tumour cell lines were established in vitro from 16 cases of Epstein-Barr (EB) virus genome-positive Burkitt's lymphoma (BL), 7 of "endemic" origin (i.e. from holoendemic malarial areas of Africa and of New Guinea) and 9 of "sporadic" origin (i.e. from outside such high-incidence areas). All the BL cell lines thus established were monoclonal by immunoglobulin isotype expression and displayed a characteristic chromosomal translocation, t(8:14) or t(8:22), confirming their malignant origin. Clear differences observed between the individual BL cell lines appeared to be related to their endemic or sporadic status. All 7 endemic cell lines began growth as a carpet of single cells, often with small, loose clumps appearing in later passage. Whilst 3 lines of sporadic origin displayed a similar pattern to the above, the majority of sporadic lines grew as large, tight clumps of cells from the first passage onwards. These differences in growth pattern were reflected by differences in cell surface phenotype, as defined in indirect immunofluorescence tests using a panel of monoclonal antibodies (MAbs) specific for B-lineage-associated antigens. BL cell lines could be classified into 3 separate groups on the basis of their reactivity with 6 particular antibodies (MHM6, AC2, Ki-1, Ki-24, J5 and 38.13). All 7 endemic BL cell lines and 2 of the 3 sporadic BL cell lines which began growth as single cells showed a group-I cell-surface phenotype (MHM6, AC2, Ki-1, Ki-24 negative; J5, 38.13 positive) in early passage. In contrast, all 6 sporadic BL cell lines which began growth in large clumps displayed a distinct group-II phenotype (MHM6, AC2, Ki-1 positive/negative; Ki-24, J5, 38.13 positive); in later passage most of these sporadic lines progressed to a group-III phenotype (MHM6, AC2, Ki-1, Ki-24 positive; J5, 38.13 negative) without loss of those immunoglobulin and chromosomal markers identifying the cells' malignant origin. These clear differences between endemic BL cell lines on the one hand and the majority of sporadic BL cell lines on the other suggest that endemic BL arises from a more restricted range of progenitor B cells than does the sporadic form of the disease.

Modelling and Residual Analysis of Nonlinear Autoregressive Time Series in Exponential Variables

Abstract: : An approach to modelling and residual analysis of nonlinear autoregressive time series in exponential variables is presented; the approach is illustrated by analysis of a long series of wind velocity data which has first been detrended and then transformed into a stationary series with an exponential marginal distribution The stationary series is modelled with a newly developed type of second order autoregressive process with random coefficients, called the NEAR(2) model; it has a second order autoregressive correlation structure but is nonlinear because its coefficients are random The exponential distributional assumptions involved in this model highlight a very broad four parameter structure which combines five exponential random variables into a sixth exponential random variable; other applications of this structure are briefly considered Dependency in the NEAR(2) process not accounted for by standard autocorrelations is explored by developing a residual analysis for time series having autoregressive correlation structure; this involves defining linear uncorrelated residuals which are dependent, and then assessing this higher order dependence by standard time series computations Application of this residual analysis to the wind velocity data illustrates both the utility and difficulty of nonlinear time series modelling

Stromal cell types in the developing thymus of the normal and nude mouse embryo

Abstract: The anatomical distribution of various nonlymphoid cell types in the embryonic mouse thymus in vivo and in vitro, as well as in the thymic rudiment of the nude mouse embryo, has been studied. For this purpose a panel of monoclonal antibodies, ER-TR3, 4, 5, 6 and 7, directed to various types of stromal cells of the mouse thymus, was used in combination with immunoperoxidase labeling on frozen sections. It was shown that as early as day 13 in thymic ontogeny distinction of TR4+ cortical epithelial cells and TR5+ medullary epithelial cells is possible. Thus, as far as stromal components are concerned, the thymus at day 13 in ontogeny is already subdivided into cortex and medulla. At day 13, Ia (TR3) was expressed in a focal pattern in the medulla subsequently appearing throughout both cortex and medulla by day 16. The thymic rudiment of the nude mouse embryo differs markedly from the normal embryonic thymus in its lack of demonstrable Ia antigen. Furthermore, TR4 and TR5 were only expressed on occasional epithelial cells lining the cysts of the nude thymus in a mutually exclusive fashion. The majority of stromal cells of the nude thymus, however, is negative for all ER-TR antibodies tested. In addition, we have shown that in organ cultures the organization of the stroma of thymic lobes remains intact, at least for a period of 11 days. Embryonic thymi cultured in the presence of deoxyguanosine, which causes depletion of lymphoid cells, also contain cortical and medullary areas as identified by the presence of TR3,4+ and TR5+ stromal cells. This indicates that the lack of organization in the nude thymus is not simply due to the absence of lymphoid cells.