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Biomedical subjects

H M Cooper

Publications and source records attributed to H M Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1994

A new surgical approach to the ram suprachiasmatic nuclei.

In mammals, lesions of the suprachiasmatic nuclei (SCN) cause alterations in several biological rhythms. Investigation of the role of the ovine SCN requires complete bilateral lesions of the nuclei. However, the elongated shape, location and horizontal orientation of this hypothalamic structure prohibit a classical stereotaxic vertical approach. We present here a new trans-sinusal surgical technique to reach the SCN for lesion or other studies, which avoids damage to hypothalamic or other structures. The surgical procedure allows direct viewing of the SCN, located dorsal to the optic chiasm on the rostro-ventral surface of the brain. The orientation of the access tunnel is roughly aligned with the nearly horizontal main axis of the nuclei. An example of the use of such a surgical procedure is described: the bilateral destruction of the SCN. Following surgery, the extent of lesions was assessed by histology, showing complete destruction of the SCN. In order to demonstrate the physiological effects of the lesions, melatonin secretion profiles were followed over 48 h periods and compared before and after surgery. Bilateral SCN lesions induced alterations in the rhythm of melatonin secretion: levels were no longer correlated with light/dark cycles.

Animals↗
PubMed1994

Neuroanatomical pathways linking vision and olfaction in mammals.

Retinal projections to several telencephalic structures have been demonstrated in a wide range of mammalian species following intraocular injections of tritiated amino acids and cholera toxin subunit-B conjugated to horseradish peroxidase. Since these regions are also innervated by olfactory fibers, we investigated the distribution of convergent projections using simultaneous injections of different anterograde tracers in the eye and olfactory bulbs. Convergent projections from the retina and from the olfactory bulbs were observed in the piriform cortex, olfactory tubercle, the cortical region of the medial amygdala, lateral hypothalamus, and the bed nucleus of the stria terminalis. A few retinal fibers also invade the nucleus of the lateral olfactory tract, the bed nucleus of the accessory olfactory bulb and the diagonal band of Broca. Injections of retrograde tracers in the medial amygdala, the bed nucleus or the lateral hypothalamus shows that the visuo-olfactory convergence mainly involves projections originating from the accessory olfactory bulb, and to a lesser extent from the ventromedial region of the main olfactory bulb. Fewer than 20 retinotelencephalic ganglion cells were identified in the retina, mainly located contralateral to the injection site. Ganglion cells were medium sized and possessed two long slender opposing dendrites. These retinal and olfactory projections could provide an anatomical substrate for the modulation of gonadotropin hormone levels and the olfactory influence on light mediated rhythms related to reproductive physiology.

Animals↗
PubMed1993

Visual system of a naturally microphthalmic mammal: the blind mole rat, Spalax ehrenbergi.

Retinal projections and visual thalamo-cortical connections were studied in the subterranean mole rat, belonging to the superspecies Spalax ehrenbergi, by anterograde and retrograde tracing techniques. Quantitative image analysis was used to estimate the relative density and distribution of retinal input to different primary visual nuclei. The visual system of Spalax presents a mosaic of both regressive and progressive morphological features. Following intraocular injections of horseradish peroxidase conjugates, the retina was found to project bilaterally to all visual structures described as receiving retinal afferents in non-fossorial rodents. Structures involved in form analysis and visually guided behaviors are reduced in size by more than 90%, receive a sparse retinal innervation, and are cytoarchitecturally poorly differentiated. The dorsal lateral geniculate nucleus, as defined by cyto- and myelo-architecture, cytochrome oxidase, and acetylcholinesterase distribution as well as by afferent and efferent connections, consists of a narrow sheet 3-5 neurons thick, in the dorsal thalamus. Connections with visual cortex are topographically organized but multiple cortical injections result in widespread and overlapping distributions of geniculate neurons, thus indicating that the cortical map of visual space is imprecise. The superficial layers of the superior colliculus are collapsed to a single layer, and the diffuse ipsilateral distribution of retinal afferents also suggests a lack of precise retinotopic relations. In the pretectum, both the olivary pretectal nucleus and the nucleus of the optic tract could be identified as receiving ipsilateral and contralateral retinal projections. The ventral lateral geniculate nucleus is also bilaterally innervated, but distinct subdivisions of this nucleus or the intergeniculate leaflet could not be distinguished. The retina sends a sparse projection to the dorsal and lateral terminal nuclei of the accessory optic system. The medial terminal nucleus is not present. In contrast to the above, structures of the "non-image forming" visual pathway involved in photoperiodic perception are well developed in Spalax. The suprachiasmatic nucleus receives a bilateral projection from the retina and the absolute size, cytoarchitecture, density, and distribution of retinal afferents in Spalax are comparable with those of other rodents. A relatively hypertrophied retinal projection is observed in the bed nucleus of the stria terminalis. Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub-paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗
PubMed1993

Picosecond neodymium:yttrium lithium fluoride laser sclerectomy.

The picosecond neodymium:yttrium lithium fluoride laser, a high-power, short-pulse laser that uses low energy per pulse and has a high repetition rate and a highly coherent energy source of 1,053 nm, was used to perform sclerectomies by an ab externo approach in human cadaver eyes. We evaluated laser settings with regard to full-thickness scleral perforation and thermal damage to surrounding tissue. We studied energy per pulse, depth per burst (a present number of spots), spot and line separation of the pattern (spacing between spots of the laser in length [spot separation] and width [line separation]), and total energy required to perforate the sclera. Efficiency was determined by evaluating which settings required the fewest spots and least total energy to perforate the sclera. We studied histologic sections of the sclerectomy sites to determine thermal damage to the surrounding sclera. The picosecond neodymium:yttrium lithium fluoride laser is effective in performing full-thickness sclerectomy with minimal thermal damage to the surrounding tissue. The anterior chamber could be penetrated with an average total energy of 13.3 +/- 0.4 (SEM) J. The sclerectomy size was 545 +/- 11 microns externally and 163 +/- 4 microns internally. Successful sclerectomies were performed with as little as 3 to 5 microns of thermal damage to the surrounding scleral tissue with 250 microJ per pulse.

Cadaver↗
PubMed1993

Ocular regression conceals adaptive progression of the visual system in a blind subterranean mammal.

The mole rat, Spalax ehrenberghi, is an extreme example of natural visual degeneration in mammals: visual pathways are regressed and incomplete, and the absence of visual cortical potentials or an overt behavioural response to light have led to the conclusion that Spalax is completely blind. But structural and molecular investigations of the atrophied, subcutaneous eye suggest a functional role for the retina in light perception, and entrainment of circadian locomotor and thermoregulatory rhythms by ambient light demonstrates a capacity for photoperiodic detection. We report here that severe regression of thalamic and tectal structures involved in form and motion perception is coupled to a selective hypertrophy of structures subserving photoperiodic functions. As an alternative to the prevalent view that ocular regression results from negative or nonselective evolutionary processes, the differential reduction and expansion of visual structures in Spalax can be explained as an adaptive response to the underground environment.

Adaptation, Physiological↗
PubMed1991

Cell type-specific integrin variants with alternative alpha chain cytoplasmic domains.

The integrin heterodimers composed of the alpha 6 subunit with the beta 1 or beta 4 subunit (alpha 6 beta 1 and alpha 6 beta 4) are receptors for laminin and basement membrane components, respectively. The alpha 3 beta 1 integrin recognizes laminin, collagen, fibronectin, or epiligrin. We report the identification of structural variants (A and B) of the alpha 6 and alpha 3 subunits, containing distinct cytoplasmic domains. The expression of one cytoplasmic domain or the other, based probably on alternative exon usage, is cell-type dependent. Most transformed cell lines express both alpha 6A and alpha 6B isoforms, as determined by mRNA amplification or antibody immunoprecipitation. In contrast, embryonic fibroblasts express exclusively alpha 6A, and embryonic stem cells express exclusively alpha 6B. In most normal tissues, both alpha 6 isoforms are detectable, but several tissues express either alpha 6A or alpha 6B. The alpha 3B mRNA was amplified from heart and brain, while all other tissues and cell lines tested contained only alpha 3A mRNA. Alternative cytoplasmic domains may provide a means for varying the cellular responses to the ligands of alpha 6 and alpha 3 integrins according to the cell type.

Amino Acid Sequence↗
PubMed1991

The major laminin receptor of mouse embryonic stem cells is a novel isoform of the alpha 6 beta 1 integrin.

Laminin is the first extracellular matrix protein expressed in the developing mouse embryo. It is known to influence morphogenesis and affect cell migration and polarization. Several laminin receptors are included in the integrin family of extracellular matrix receptors. Ligand binding by integrin heterodimers results in signal transduction events controlling cell motility. We report that the major laminin receptor on murine embryonic stem (ES) cells is the integrin heterodimer alpha 6 beta 1, an important receptor for laminin in neurons, lymphocytes, macrophages, fibroblasts, platelets and other cell types. However, the cytoplasmic domain of the ES cell alpha 6 (alpha 6 B) differs totally from the reported cytoplasmic domain amino acid sequence of alpha 6 (alpha 6 A). Comparisons of alpha 6 cDNAs from ES cells and other cells suggest that the alpha 6 A and alpha 6 B cytoplasmic domains derive from alternative mRNA splicing. Anti-peptide antibodies to alpha 6 A are unreactive with ES cells, but react with mouse melanoma cells and embryonic fibroblasts. When ES cells are cultured under conditions that permit their differentiation, they become positive for alpha 6 A, concurrent with the morphologic appearance of differentiated cell types. Thus, expression of the alpha 6 B beta 1 laminin receptor may be favored in undifferentiated, totipotent cells, while the expression of alpha 6 A beta 1 receptor occurs in committed lineages. While the functions of integrin alpha chain cytoplasmic domains are not understood, it is possible that they contribute to transferring signals to the cell interior, e.g., by delivering cytoskeleton organizing signals in response to integrin engagement with extracellular matrix ligands. It is therefore reasonable to propose that the cellular responses to laminin may vary, according to what alpha subunit isoform (alpha 6 A or alpha 6 B) is expressed as part of the alpha 6 beta 1 laminin receptor. The switch from alpha 6 B to alpha 6 A, if confirmed in early embryos, could then be of striking potential relevance to the developmental role of laminin.

Amino Acid Sequence↗
PubMed1991

A function for the integrin alpha 6 beta 4 in the hemidesmosome.

Many epithelial cells appear to use cell-substratum adhesion complexes known as hemidesmosomes as the main means of anchorage to the connective tissue. Initially recognized as distinctive electron-dense images, hemidesmosomes are still poorly understood at the biochemical level. The regulation and mode of their assembly, which is disrupted in certain blistering diseases and is critical to proper wound repair, also remains to be elucidated. The integrin alpha 6 beta 4 is expressed along the basal surface of various epithelial cells. We show here that this integrin localizes to hemidesmosomes as determined by immunoelectron microscopy using antibodies directed against both the extra- and intracytoplasmic domains of alpha 6 beta 4. This result, which agrees with a recent study, suggests a functional role for the alpha 6 beta 4 integrin in the hemidesmosomes. We therefore investigated such a potential role for this integrin using the cultured rat bladder carcinoma cell line 804G, which has the uncommon ability to form hemidesmosomes in vitro when maintained on uncoated glass substrates. By immunoprecipitation and immunofluorescence, we show that 804G cells express alpha 6 beta 4 along their basal surface in a punctate pattern that overlaps with the distribution of hemidesmosomal plaque antigens. However, this pattern is altered when cells are plated in the presence of an antiserum directed against alpha 6 beta 4. Furthermore, no hemidesmosomes are detectable at the ultrastructural level in the alpha 6 beta 4 antibody-treated cells compared with control cells. These results indicate that integrins may play a critical role in assembly and adhesive functions of the hemidesmosome.

Animals↗
PubMed1991

Distribution of the alpha 1-alpha 6 integrin subunits in human developing and term placenta.

The distribution of the alpha 1-alpha 6 as well as alpha v, beta 1, beta 3 and beta 4 integrin subunits in human first and second trimester and term placentas was studied by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (mAbs). In first and second trimester villi, the alpha 1 and beta 1 integrin subunits were detected in the stromal cells, that were mostly also immunoreactive for desmin. Desmin-positive stromal cells were also found in villi of term placentas, but the stroma was negative for anti-alpha 1 and -beta 1. In the villous trophoblast, anti-alpha 6 and -beta 4 revealed a distinct basal immunoreactivity during all stages of development, whereas immunoreactivity for the alpha 3 and beta 1 subunits emerged during the second and third trimesters. Throughout placental development, endothelia of villous capillaries reacted prominently with anti-alpha 1 and -beta 1. Intermediate trophoblastic cells displayed a somewhat heterogenous immunoreactivity for the beta 1, alpha 1, alpha 3 and alpha 5 integrin subunits, and differed from villous trophoblast also in their lack of expression of the alpha 6 and beta 4 subunits. While nondecidualized endometrial cells displayed weak reactivity for the alpha 1 and beta 1 integrin subunits, the individual decidual cells presented both a basement membrane and a cell surface-confined immunoreactivity for anti-alpha 1, -alpha 3, and -beta 1. The results suggest a role for integrins in placental development, and show that expression of integrins is modulated during the differentiation of trophoblast, villous stroma, and decidual cells. Furthermore, the basal localization of alpha 6 beta 4 and alpha 3 beta 1 integrins suggests that they are employed as basement membrane receptors in the villous trophoblast, and the emergence of the alpha 3 beta 1 complex may reflect that the cytotrophoblast and syncytiotrophoblast recognize the basement membrane differently.

Capillaries↗
PubMed1990

Macaque accessory optic system: I. Definition of the medial terminal nucleus.

The organization of the accessory optic system (AOS) has been studied in the macaque monkey following intravitreal injections of tritiated amino acids in one eye. Retinal projections to the dorsal (DTN) and the lateral (LTN) terminal nuclei are identical to those previously described in other primate species. We observed an additional group of retinorecipient cells of the AOS, located between the cerebral peduncle and the substantia nigra, which we define as the interstitial nucleus of the superior fasiculus, medial fibers. In this report, we focus our attention on the medial terminal nucleus (MTN). Although a ventral division of this nucleus (MTNv) was not observed in the macaque, the retina projects to a group of cells in the midbrain reticular formation (MRF), which we argue to be homologous to the dorsal division of the MTN (MTNd). To provide evidence in support of this homology, the retinal projection to the MTNv and MTNd was also examined in 21 additional species from 11 orders of mammals including carnivores, marsupials, lagomorphs, rodents, bats, insectivores, tree shrews, hyraxes, pholidotes, edentates, and five additional species of primates. Whereas the retina projects to both ventral and dorsal divisions in all species studied, in haplorhine primates only the projection to the MTNd is conserved. The relative topological position of the MTNd in the MRF, dorsomedial to the substantia nigra and ventrolateral to the red nucleus, remains constant throughout the mammals. The trajectory of fiber paths innervating the MTNd is also similar in all species. In addition, the MTNd has comparable afferent and efferent connections with retina, pretectum, and vestibular nuclei in all species thus far studied. These results support the unequivocal conclusion that the MTNd is an unvarying feature of the mammalian AOS.

Animals↗
PubMed1990

Macaque accessory optic system: II. Connections with the pretectum.

Connections of the accessory optic system (AOS) with the pretectum are described in the macaque monkey. Injections of tritiated amino acids in the pretectum demonstrate a major contralateral projection to the dorsal (DTN), lateral (LTN), and medial (MTN) terminal nuclei of the AOS and a sparser projection to the ipsilateral LTN. Injections of retrograde tracers, Fast Blue (FB), or wheat germ agglutinin horseradish peroxidase (WGA-HRP) plus nonconjugated horseradish peroxidase (HRP) in the LTN show that the pretectal-LTN projection originates from two nuclei. The main source of pretectal efferents to the LTN is from the pretectal olivary nucleus (OPN) and is entirely contralateral. This projection, which appears unique to primates, originates from the large multipolar cells of the OPN. In addition to this projection, the nucleus of the optic tract (NOT) projects to the ipsilateral LTN, as in nonprimates. Injection of WGA-HRP in the pretectum shows a reciprocal predominantely ipsilateral projection from the LTN to the pretectum. Retinas were observed after injection of FB in the LTN. The retinal ganglion cells projecting to the AOS are mainly distributed near the fovea and in the nasal region of the contralateral eye, suggesting a nasotemporal pattern of decussation. The demonstration of a direct connection between LTN and OPN forces to a reconsideration of the functional role of the AOS. Previous descriptions of luminance responsive cells in the LTN support a possible participation of this nucleus in the control of the pupillary light reflex.

Amidines↗
PubMed1990

Effects of alcohol on human aggression: an integrative research review.

This review used quantitative and qualitative techniques to integrate the alcohol and aggression literature. The primary purpose of the review was to determine if a causal relation exists between alcohol and aggression. The main meta-analysis included 30 experimental studies that used between-subjects designs, male confederates, and male subjects who were social drinkers. Studies using other designs or subject populations were integrated with meta-analytic procedures when possible and summarized descriptively when not. The results of the review indicate that alcohol does indeed cause aggression. However, alcohol effects were moderated by certain methodological parameters.

Aggression↗
PubMed1990

Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.

Amino Acid Sequence↗
PubMed1989

Phylogenetic relations between microbats, megabats and primates (Mammalia: Chiroptera and Primates).

We examine the paraphylectic hypothesis of bat origins, both in the light of previous discussions, and in the light of new evidence from our analyses of neurological traits and wing morphology. Megabats share with primates a variety of complex details in the organization of neural pathways that have not been found in any other mammalian group, particularly not in microbats. The features previously used to link microbats and megabats have been examined and found to be questionable bases for support of a monophyletic origin. In particular, morphological analyses of the musculoskeletal adaptations associated with the flight apparatus are consistent with two separate origins of the mammalian wing. Taken together, these analyses suggest that megabats evolved from an early branch of the primate lineage. This branch was comprised of moderate-sized, phytophagous gliders, of which the other living descendants are the dermopterans. Microbats, in contrast, probably evolved much earlier from small, agile insectivores whose forelimbs had long metacarpals in relation to their phalanges.

Animals↗
PubMed1989

Retinohypothalamic pathway: a breach in the law of Newton-Müller-Gudden?

Theories of binocular vision originally imagined by Newton provided the foundation for subsequent investigations of the visual system by early anatomists and physiologists. These studies led to the widely accepted concept that degree of optic fiber decussation in the chiasm is inversely related to frontal orientation of the optical axes of the eyes (law of Newton-Müller-Gudden). A survey of 23 species from 11 mammalian orders demonstrates that, in contrast to other visual pathways, the retinohypothalamic projection does not obey this general principle. In further contradiction, an unexpected finding in primates is the predominance of ipsilateral, rather than contralateral, retinal input to the suprachiasmatic nucleus. This unusual organization underlines the functional and evolutionary specificities of this 'non-image forming' visual pathway.

Animals↗
PubMed1989

A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells.

Carcinoma cells express a novel integrin involved in cell adhesion to vitronectin, but not to fibrinogen or von Willebrand factor, whereas melanoma and endothelial cells express a vitronectin receptor (alpha v beta 3) that promotes cell attachment to all of these matrix components. The integrin responsible for this adhesive phenotype of carcinoma cells is composed of an alpha subunit that is indistinguishable from the alpha v of the vitronectin receptor and a beta subunit (beta x) that is distinct from any known integrin beta subunit. Accordingly, Northern blot analysis identifies an mRNA for alpha v, but not for beta 3 in carcinoma cells. This receptor appears to mediate cell adhesion to vitronectin as well as fibronectin since an antibody directed to its alpha subunit blocked carcinoma cell adhesion to both of these matrix proteins. These results suggest that homologous integrins with identical alpha subunits and structurally distinct beta subunits can account for the functional recognition of different matrixes by two cell types.

Adenocarcinoma↗
PubMed1989

Retinal projection to mammalian telencephalon.

Retinal projections were studied in species from 8 orders of mammals using anterograde tracing techniques. The olfactory tubercle of basal telencephalon receives a projection from the retina in all animals. In all species the course of labelled fibers is similar and the terminal distribution of label along the internal border of the granular cell layer is restricted to the mediocaudal region of the tubercle. These shared characteristics suggest that this pathway is a typical mammalian feature, possibly providing for convergence of visual and chemosensory information in telencephalon.

Animals↗