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H M Cooper

Publications and source records attributed to H M Cooper.

70 records · Page 4Linked to original sources
PubMed1989

The autoantigenic response to rabbit cytochrome c.

In this report we describe the production and characterization of autoantibody responses to rabbit cytochrome c (cyt c) in rabbits immunized with either the native monomeric or polymerized form of rabbit cyt c. Fine-specificity analyses of the response indicated that the majority of the response was to the evolutionarily conserved amino-terminal region of the molecule. The relative affinity of the autoantibody interaction with rabbit cyt c was assessed by a solid-phase assay and was found to be lower than that observed for rabbit anti-horse cyt c antibody populations. These findings are consistent with the prediction that low-affinity self-reactive B cells may escape tolerance induction.

Amino Acid Sequence↗
PubMed1988

The heme moiety of cytochrome c is an autoreactive Ir gene-restricted T cell epitope.

In these studies, we have shown that the heme moiety of cyt c is a dominant T cell epitope that induces a large proliferative response in lymph node T cells derived from SJL and B10.A mice when presented on either unfixed or fixed syngeneic APCs. Not only is this vigorous response observed for cyt c-primed T cell populations but also for populations obtained from naive SJL or B10.A mice. The reactivity to the heme moiety falls under strict MHC restriction, in that it is present only in murine strains bearing either the I-Ak or I-As molecule and can be blocked by antibodies specific for these class II molecules. Therefore, these findings require that the current models describing the nature of T cell epitopes be extended to include nonpeptide molecules. Furthermore, as the heme moiety is ubiquitous throughout the organism, although sequestered within proteins, the existence of heme-reactive T cell populations in unprimed animals provides another example of the existence of self-reactive T cell clones.

Animals↗
PubMed1987

Site-directed chemical modification of horse cytochrome c results in changes in antigenicity due to local and long-range conformational perturbations.

Comparative binding studies with peptide fragments of the whole antigen, or with evolutionarily related intact proteins with varying degrees of sequence homology, have been used extensively to map antigenic sites on proteins to the resolution of single amino acid residues. These methods are limited, however, since high affinity antibodies will often not react with peptides and evolutionarily related proteins are available for only a few antigens. In this study we use site-directed chemical modification of horse cytochrome c to identify residues involved in the binding sites of four monoclonal antibodies specific for this protein. Thus, we have N-formylated the single tryptophan found in horse cytochrome c at position 59 and N-carbethoxylated one of the histidyl residues, which was determined to be at position 26 by the analysis of proteolytic cleavage fragments of the modified protein using liquid secondary ion-mass spectrometry on triple quadropole or tandem quadropole Fourier transform instruments. We discuss the impact of these modifications on the antigenicity of horse cytochrome c with regard to the conformational perturbations introduced by such modifications and with reference to our previous studies on the binding sites of these antibodies using other methodologies (Jemmerson, R., and Paterson, Y. (1986) BioTechniques 4, 18-31).

Animals↗
PubMed1987

Accessory optic system of an anthropoid primate, the gibbon (Hylobates concolor): evidence of a direct retinal input to the medial terminal nucleus.

The accessory optic system (AOS) was studied in an anthropoid primate by using anterograde transport of tritiated amino acids and autoradiographic techniques. The course of the accessory optic tract (AOT) and the retinal projection to the terminal nuclei are described in the gibbon and compared to that of other mammals. The AOT consists of a superior fasciculus, which includes both an anterior and a posterior fiber branch. An inferior fasciculus of the AOT is absent. In contrast to previous reports in haplorhine primates, which describe the AOS as consisting of only the dorsal (DTN) and the lateral (LTN) terminal nuclei, we find that in the gibbon, three cellular groups receive a bilateral projection, predominantly from the contralateral retina. According to cytoarchitecture and topographic location, two of these nuclei correspond to the DTN and the LTN. The third cellular group, situated dorsomedial to the substantia nigra, receives a distinct retinal projection and extends rostrocaudally for 2.0 mm in the mesencephalon. This nucleus is homologous to the dorsal division of the medial terminal nucleus (MTN) in other mammals. There was no evidence for a ventral division of the MTN, which in nonprimates is typically situated at the ventromedial base of the cerebral peduncle. Examination of brain morphology in primates suggests that the ventral division of the MTN has been displaced from its phylogenetically stable location in the medial part of the ventral midbrain to a more dorsal position. This shift appears to be a consequence of the overall morphological influences resulting from the relative enlargement of the pons in this region. The demonstration of a direct retinal projection to the MTN in the gibbon, as well as recent reports in other primates, indicates that a complete AOS consisting of three terminal nuclei is a feature common to all mammals.

Animals↗
PubMed1986

The accessory optic system in a prosimian primate (Microcebus murinus): evidence for a direct retinal projection to the medial terminal nucleus.

The accessory optic system (AOS) was studied in the prosimian primate, Microcebus murinus, by using intraocular injections of the anterograde tracers 3H-proline and horseradish peroxidase (HRP). Retinal fibers were found to terminate bilaterally in all three mesencephalic AOS nuclei as defined by Hayhow ('66, J. Comp. Neurol. 126:653-672). In contrast to previous reports in primates, we find that both the ventral and dorsal divisions of the medial terminal nucleus (MTN) receive projections from the retina. The ventral MTN is composed of a compact triangular group of cells, situated at the medial base of the cerebral peduncle, rostral to the rootlets of the third cranial nerve. The dorsal MTN extends dorsomedial to the substantia nigra and is composed of characteristic fusiform cells embedded in a fibrous neuropil. Although the cells of the dorsal MTN intermingle somewhat with the nigral cells, the nucleus is clearly distinguished by cyto- and myeloarchitectural features. The large lateral terminal nucleus (LTN) receives a dense projection from the retina and forms a prominent bulge on the lateral surface of the cerebral peduncle. The dorsal terminal nucleus (DTN) is located between the brachia of the superior and inferior colliculi, near the origin of the superior fasciculus of the accessory optic tract (AOT). This fasciculus is composed of anterior, middle, and posterior branches. In addition, a ventral group of fibers, corresponding to the inferior fasciculus of the AOT previously described in nonprimates, was identified in all planes of section. The results confirm the existence of a common plan of AOS organization in mammals.

Adaptation, Biological↗
PubMed1986

Antibody response to the C-terminal peptide sequence in beef myoglobin.

The nature of the surface determinants on the beef myoglobin molecule which direct the distinctive antibody response of sheep, have been further defined. Antisera raised to beef myoglobin in sheep, rabbits and mice have been compared for their ability to recognize the synthetic C-terminal beef myoglobin peptide (140-153), which contains four of the six amino acid substitutions between sheep and beef myoglobins. The antibodies raised in rabbits, directed to the entire surface of beef myoglobin, contain only a minor population directed to the C-terminal sequence: in mice, even fewer antibodies are specific for this sequence. In sheep, however, antibodies to beef myoglobin appear to be directed almost exclusively to topographic domains which include the (140-153) sequence. This specificity is most apparent in "early" antisera in which all antibodies display equal avidity for "native" beef myoglobin and the peptide; further immunization produces antibodies which recognize a larger overlapping set of domains and only 20% of these antibodies have effective avidity for the (140-153) peptide. The antibodies to beef myoglobin raised in sheep comprise two discrete populations. One ("common") population is directed to regions of similarity between the beef and sheep myoglobin molecules, in which the region represented by the C-terminal peptide of beef myoglobin is less important in defining the antibody-binding site and/or affinity, while still being directly involved in the topographic determinant. The other ("non-common") appears to be directed almost exclusively to the C-terminal sequence (140-153) of beef myoglobin. The findings are discussed in relation to our previous findings on the effect of the host species on the nature of the antibody response and in relation to views on the possibility of direct vs indirect effects of evolutionary amino acid substitution on immuno-cross-reactivity among homologous proteins.

Animals↗
PubMed1985

Influence of female odors on lateral hypothalamus in the male rat. Semiquantitative deoxyglucose analysis.

The uptake of 14C deoxyglucose (2DG) has been studied in various hypothalamic and limbic structures of male rats exposed to female odors. Uptake differences were visualized by image processing and quantified by measurement of optical density ratios. With respect to the control group, an increase in uptake was observed in the lateral hypothalamic area (LHA), not only in the olfactory bundle, but also, and more obviously, in the parafornical part. This 2DG response is not a result of an odor-induced general motor activation, although it seems to depend on the behavioral reaction of the animal towards the odor. A similar correspondence was not observed for the 2DG response to odor in the ventromedial hypothalamus. Observations in the medial preoptic area, in the corticomedial amygdala, in the lateral septum, or in the dorsomedial hypothalamus did not reveal any significant change in 2DG uptake.

Animals↗
PubMed1985

Original antigenic sin and the production of autoantibodies.

Autoantibodies to sheep myoglobin have been raised by priming sheep with beef myoglobin and boosting with sheep myoglobin. The autoantibodies appear to be a subset of those produced when beef myoglobin is used for both priming and boosting. This subset of antibodies is presumably directed to the surface regions which are common to both myoglobins. The antibodies which bind to sheep myoglobin in the 2 types of antisera differ. Those elicited by boosting with beef myoglobin bind better to beef myoglobin than to sheep myoglobin, while those obtained by boosting with sheep myoglobin bind with equal avidity to the 2 myoglobins. It would seem therefore that the boosting immunogen determines which fraction of antibodies is selected from the antibody repertoire established by the priming immunogen. Our results also show that tolerance at the T-cell level can be circumvented by exposing the immune system to a protein closely related to a homologous self protein.

Animals↗
PubMed1984

Antibody response to myoglobins: effect of host species.

Using both direct and competitive binding studies it is demonstrated that antibodies to beef myoglobin raised in sheep are able to distinguish between beef and sheep myoglobins although these two proteins differ by only six of the 153 amino acid residues. By contrast, antibodies to beef myoglobin raised in rabbits, dogs and chickens bind almost equally well to beef and sheep myoglobins. It is also shown that antibodies to beef myoglobin raised in sheep have a lower avidity for beef myoglobin than do antibodies raised in more distantly related species. Furthermore, only 50% of the specific anti-beef myoglobin antibodies isolated from sheep antisera will bind to sheep myoglobins whereas 100% of the specific antibodies isolated from the antisera of the other immunised species will bind to sheep myoglobin. It is suggested that antibodies to beef myoglobin are raised to those surface regions which are topographically altered as a result of sequence differences from the host's own myoglobin. When the host animal is evolutionarily distant these sequence differences are considerable and antibodies are raised to the entire surface of the molecule. However, when the host's myoglobin is very similar in sequence to beef myoglobin (as is the case when using sheep as the host animal) antibodies are made only to surface regions affected by the sequence differences. Some of these antibodies--those to the regions of greatest difference--will bind weakly if at all to sheep myoglobin, while those directed to areas of lesser difference will bind well to sheep myoglobin.

Adsorption↗
PubMed1983

Drug treatment of hyperactivity in children.

Recently-developed quantitative reviewing procedures were applied to 61 selected studies in order to explore the efficacy of pharmacological management for children identified as hyperactive. Analysis of effect-size information derived from the studies revealed that the average child receiving drug treatment was less hyperactive than 88.5 per cent of the control children. 30 per cent of this effect could be attributed to placebo phenomenon. The analysis also indicated that drug therapy had the most pronounced effect on dependent variables consisting of standardized or informal measures of behaviour and the least effect on measures of IQ and academic achievement. The advantages of quantitative reviewing methodology for adding clarity and consensus to complex bodies of literature are demonstrated and discussed.

Analysis of Variance↗
PubMed1979

Thalamic projections to area 17 in a prosimian primate, Microcebus murinus.

Electrophysiological recording of single neurons was used to describe the representation of visual space in area 17, and the technique of retrograde transport of horseradish peroxidase (HRP) was applied to relate these results to projections from the thalamus in the prosimian primate Microcebus murinus. The visuotopic organization of area 17 was found to resemble that of other primates. On the dorsal surface, the border of area 17 corresponds to the representation of the vertical meridian. Proceeding medially across the surface the location of receptive fields descends along the vertical meridian, while moving caudally receptive fields progress temporally. Most of the dorsolateral surface is devoted to central vision and corresponds to a well developed area centralis. Following HRP injections in striate cortex, columns of labeled cells were found in the dorsal lateral geniculate (dLGN) extending orthogonally across all six layers. These columns run in a general ventrodorsal and caudorostral direction, parallel to a line connecting the cellular discontinuities corresponding to the optic disc. These discontinuities are present in magnocellular layer 1 and parvocellular layers 5 and 6, thus receiving from the nasal retina of the contralateral eye. The representation of the vertical meridian is situated in the ventromedial portion of the dLGN, and the monocular field is represented in the dorsal extremity. Anterior dLGN projects to the calcarine fissure (lower field) and posterior dLGN projects to the ventral surface of the cortex (upper field). Extrageniculate input to area 17 was found to originate from the pulvinar. HRP labeled cells were located in two distinct divisions of this nucleus, the cytoarchitecture of which is described. In addition, projections to occipital cortex were found to arise from the intralaminar nuclei.

Animals↗
PubMedDate not supplied

Ultrastructural study of the optic nerve in blind mole-rats (Spalacidae, Spalax).

The optic nerve in two species of subterranean mole-rats (Spalacidae) has been examined at the ultrastructural level. The axial length of the eye and the diameter of the optic nerve are 1.9 mm and 52.5 microns in Spalax leucodon, and 0.7 mm and 80.8 microns in Spalax ehrenbergi, respectively. An anti-glial fibrillary acidic protein postembedding procedure was used to distinguish glial cell processes from axons. In both species, the optic nerve is composed exclusively of unmyelinated axons and a spatial distribution gradient according to the size or the density of fibers is lacking. The optic nerve of S. leucodon contains 1790 fibers ranging in diameter from 0.07-2.30 microns (mean = 0.57 microns), whereas in S. ehrenbergi, only 928 fibers, with diameters of 0.04-1.77 microns (mean = 0.53 microns) are observed. In S. ehrenbergi, a higher proportion of glial tissue is present and the fascicular organization of optic fibers is less obvious. Distribution gradients according to size frequency or density of fibers in the optic nerve are absent in both species. Comparison with other mammals suggests that although ocular regression in microphthalmic species is correlated with a significant decrease in the total number of optic fibers and the relative proportion of myelinated fibers, no difference in the absolute size range of unmyelinated axons is observed. The total absence of myelinated fibers in Spalax may be related to the subcutaneous location of the eyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

A common mammalian plan of accessory optic system organization revealed in all primates.

The accessory optic system (AOS), which was described as early as 1870 by Gudden, constitutes a distinct midbrain visual pathway in all classes of vertebrates. In non-primate mammals, retinal fibres of this system project to a set of three nuclei: the dorsal (DTN), the lateral (LTN) and the medial (MTN) terminal nuclei. Whereas all AOS cells respond to the slow motion of large visual stimuli, the neurons are tuned to complementary directions of movement: horizontal temporo-nasal direction for the DTN, vertical up and down for the LTN and vertical down for the MTN. It has thus been suggested that these nuclei establish a system of retinal coordinates for the detection of whole field motion. As the AOS provides direct and indirect pathways to both oculomotor and vestibular structures, each of these nuclei is thought to be an essential link in the co-ordination of eye and head movements in relation to movement within the visual-field. One problem for the generalization of this theory is that the medial terminal nucleus has never been found in primates. In this report we establish both the existence of this nucleus and its afferent input from the retina in all major groups of primates (prosimians, New and Old World monkeys and apes), indicating a common anatomical plan of organization of the AOS in mammals.

Animals↗