Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a review of the therapeutic schedules used in our service during the past 10 years for the therapy of advanced non-small-cell lung cancer. During the first years, nonrandomized trials were conducted and several combinations were tested: MACC (methotrexate, doxorubicin, cyclophosphamide, and CCNU), cisplatin-etoposide, and cisplatin-vindesine. The results of these trials were invariably discouraging: objective responses hardly reached 30%, while the survival was around 15 months in the best case. On December 1985 a new randomized trial, based on the combination MIP (mytomicin, ifosfamide, cisplatin) was designed; 60.7% of objective responses were achieved, with 9 complete remissions (17.6%) and 22 partial remissions (43.1%). Median survival was 15 months. In order to reduce the toxicity of this combination, carboplatin was substituted for cisplatin. Unfortunately, results were very poor. No complete remission, and only 5 partial responses (20%) were achieved. At the present time, a new randomized trial is being conducted. In it, MIP combination is compared with VIP (vindesine, ifosfamide, cisplatin). Preliminary results have shown no differences between both arms in response, toxicity, or survival. New therapeutic approaches, as neoadjuvant therapy, are being explored.
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PMID:Non-small-cell lung cancer (NSCLC): chemotherapy in advanced disease. Our experience in ten years. 838 16

We have examined the origin and topography of cortical projections to area PO, an extrastriate visual area located in the parieto-occipital sulcus of the macaque. Distinguishable retrograde fluorescent tracers were injected into area PO at separate retinotopic loci identified by single-neuron recording. The results indicate that area PO receives retinotopically organized inputs from visual areas V1, V2, V3, V4, and MT. In each of these areas the projection to PO arises from the representation of the periphery of the visual field. This finding is consistent with neurophysiological data indicating that the representation of the periphery is emphasized in PO. Additional projections arise from area MST, the frontal eye fields, and several divisions of parietal cortex, including four zones within the intraparietal sulcus and a region on the medial dorsal surface of the hemisphere (MDP). On the basis of the laminar distribution of labeled cells we conclude that area PO receives an ascending input from V1, V2, and V3 and receives descending or lateral inputs from all other areas. Thus, area PO is at approximately the same level in the hierarchy of visual areas as areas V4 and MT. Area PO is connected both directly and indirectly, via MT and MST, to parietal cortex. Within parietal cortex, area PO is linked to particular regions of the intraparietal sulcus including VIP and LIP and two newly recognized zones termed here MIP and PIP. The wealth of connections with parietal cortex suggests that area PO provides a relatively direct route over which information concerning the visual field periphery can be transmitted from striate and prestriate cortex to parietal cortex. In contrast, area PO has few links with areas projecting to inferior temporal cortex. The pattern of connections revealed in this study is consistent with the view that area PO is primarily involved in visuospatial functioning.
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PMID:Topographical organization of cortical afferents to extrastriate visual area PO in the macaque: a dual tracer study. 245 34

Parietal cortex contains multiple representations of visual space. Single neurons in area LIP encode attended locations relative to the fovea, while some VIP neurons encode stimulus location relative to the head and some MIP neurons may encode location relative to the arm. These multiple representations are tailored to guide specific kinds of actions: eye movements, head movements and arm movements, respectively. The function of parietal cortex is to signal the location of attended objects relative to the observer. It does so in order to allow the organism to act on its environment. The many different kinds of actions that can be performed are likely to be supported by these very different kinds of spatial representations.
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PMID:Spatial representations for action in parietal cortex. 904 76

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.
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PMID:Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex. 1051 Jan 99

The mechanism through which VIP prevents neurotoxicity associated with HIV envelope protein has been shown to involve the release of a beta-chemokine, MIP-1 alpha. Astrocytes stimulated with subnanomolar concentrations of VIP caused the release of MIP-1 alpha and RANTES, both of which have been shown to prevent neuronal cell death associated with gp120. It is further proposed that gp120 causes neuronal cell death, in part, by competing with endogenous chemokines at various chemokines receptors in the brain that are necessary for neuronal survival. Although the chemokines are known to be mediators of inflammation, our studies suggest that these compounds have additional roles as neuroprotective agents that depend on the concentration of chemokine, cellular microenvironment, and stage of development of target neurons. Our studies further imply that in a developing system, stimulation with a MIP-1 alpha like substance is necessary for neuronal survival and interference with this action results in neuronal cell death.
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PMID:Chemokines released from astroglia by vasoactive intestinal peptide. Mechanism of neuroprotection from HIV envelope protein toxicity. 1119 13

Classic and current parcellations of the posterior parietal cortex are reviewed. Whereas earlier studies relied on subjective observation of cortical cytoarchitecture, present parcellations are mostly based on connectional and physiological criteria. These criteria have led to the identification of five areas in the intraparietal sulcus with alleged visual function: VIP, MIP, PIP, AIP, and LIP. Other visual parietal areas are 7a, in the lateral parietal surface, and, in the medial parietal wall, 7m, and V6A. Present knowledge of the dimensions, boundaries, and connections of the various visual parietal areas is uneven: whereas LIP, 7a, and 7m have been extensively explored in anatomical and physiological studies, only scant information is available for most of the intraparietal areas. It is suggested that future studies address the anatomical and functional parcellation of the posterior parietal cortex using manifold objective means of study that allow comparison by independent researchers.
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PMID:The visual parietal areas in the macaque monkey: current structural knowledge and ignorance. 1137 28

The envelope protein (gp120) of the human immunodeficiency virus produces neuronal cell death in cultures that can be prevented by co-treatment with pituitary adenylate activating peptide-38 (PACAP-38) or chemokines. To investigate the hypothesis that a functional relationship exists between these two protectants, the release of chemokines was measured in rat astrocyte cultures after PACAP-38 treatment. Chemokine analyses were performed by immunoaffinity capillary electrophoresis. Bell-shaped dose-responses for PACAP-mediated release of chemokines into the culture medium were observed with EC(50)'s of 3 x 10(15) M (RANTES: regulated upon activation normal T cell expressed and secreted), 3 x 10(-11) M (MIP-1 beta) and 10(-7)M (MIP-1 alpha). In addition, PACAP-mediated depletion of chemokines from cultured astrocytes exhibited inverted bell-shaped curves, with similar EC(50)'s to those observed for chemokine measurements of the medium. Comparative studies with structurally related peptides (vasoactive intestinal peptide [VIP] and secretin) revealed that PACAP was the most potent secretagogue for RANTES on astrocyte cultures. Gp120-mediated neuronal cell death was prevented by co-treatment with PACAP-38, although the efficacy of protection varied significantly among the gp120 isolates. A bi-model dose-response was observed with EC(50)'s of 3 x 10(-15) and 3 x 10(-11) M. Co-treatment with neutralizing antiserum to RANTES attenuated PACAP-mediated protection from toxicity associated with gp120. In contrast to previous studies with VIP and gp120 toxicity, co-treatment with anti-MIP-1 alpha did not affect PACAP-induced protection. These studies support the hypothesis that PACAP produces neuroprotection from gp120 toxicity, in part, through the release of RANTES and this mechanism is distinct from that observed with VIP.
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PMID:Chemokine release is associated with the protective action of PACAP-38 against HIV envelope protein neurotoxicity. 1237 1

We compared the cortical inputs to the superficial and deep compartments of the superior colliculus, asking if the corticotectal system, like the colliculus itself, consists of two functional divisions: visual and visuomotor. We made injections of retrograde tracer extending into both superficial and deep layers in three colliculi: the injection site involved mainly the upper quadrant representation in one case, the lower quadrant representation in a second case, and both quadrants in a third. In a fourth colliculus, the tracer injection was restricted to the lower quadrant representation of the superficial layers. After injections involving both superficial and deep layers, labeled cells were seen over V1, many prestriate visual areas, and in prefrontal and posterior parietal cortex. Both the density of labeled cells and the degree of visuotopic order as inferred from the distribution of labeled cells in cortex varied among areas. In visual areas comprising the lower levels of the cortical hierarchy, visuotopy was preserved, whereas in "higher" areas the distribution of labeled cells did not strongly reflect the visuotopic location of the injection. Despite the widespread distribution of labeled cells, there were several areas with few or no labeled cells: MSTd, 7a, VIP, MIP, and TE. In the case with an injection restricted to superficial layers, labeled cells were seen only in V1 and in striate-recipient areas V2, V3, and MT. The results are consistent with the idea that the corticotectal system consists of two largely nonoverlapping components: a visual component consisting of striate cortex and striate-recipient areas, which projects only to the superficial layers, and a visuomotor component consisting of many other prestriate visual areas as well as frontal and parietal visuomotor areas, which projects to the deep compartment of the colliculus.
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PMID:Distribution of corticotectal cells in macaque. 1285 6

The posterior parietal cortex may function as an interface between sensory and motor cortices and thus could be involved in the formation of motor plans as well as abstract representations of space. We have recorded from neurons in the intraparietal sulcus, namely, the ventral and medial intraparietal areas (VIP and MIP, respectively), and analyzed their head-movement-related signals in relation to passive and active movements. To generate active head movements, we made the animals track a moving fixation spot in the horizontal plane under head-free conditions. When under certain circumstances the animals were tracking the fixation spot almost exclusively via head movements, a clear correlation between neuronal firing rate and head movement could be established. Furthermore, a newly employed paradigm, the "replay method," made available direct comparison of neuronal firing behavior under active and passive movement conditions. In such case, the animals were allowed to make spontaneous head movements in darkness. Subsequently, the heads were fixed and the previously recorded active head-movement profile was reproduced by a turntable as passive stimulation. Neuronal responses ranged from total extinction of the vestibular signal during active movement to presence of activity only during active movement. Furthermore, in approximately one-third of the neurons, a change of vestibular on-direction depending on active versus passive movement mode was observed, that is, type I neurons became type II neurons, etc. We suggest that the role of parietal vestibular neurons has to be sought in sensory space representation rather than reflex behavior and motor control contexts.
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PMID:Vestibular signals of posterior parietal cortex neurons during active and passive head movements in macaque monkeys. 1466 66

In primates, the frontal eye field (FEF) contains separate representations of saccadic and smooth-pursuit eye movements. The smooth-pursuit region (FEFsem) in macaque monkeys lies principally in the fundus and deep posterior wall of the arcuate sulcus, between the FEF saccade region (FEFsac) in the anterior wall and somatomotor areas on the posterior wall and convexity. In this study, cortical afferents to FEFsem were mapped by injecting retrograde tracers (WGA-HRP and fast blue) into electrophysiologically identified FEFsem sites in two monkeys. In the frontal lobe, labeled neurons were found mostly on the ipsilateral side in the (1) supplementary eye field region and lateral area F7; (2) area F2 along the superior limb of the arcuate sulcus; and (3) in the buried cortex of the arcuate sulcus extending along the superior and inferior limbs and including FEFsac and adjacent areas 8, 45, and PMv. Labeled cells were also found in the caudal periprincipal cortex (area 46) in one monkey. Labeled cells were found bilaterally in the frontal lobe in the deep posterior walls of the arcuate sulcus and postarcuate spurs and in cingulate motor areas 24 and 24c. In postcentral cortical areas all labeling was ipsilateral and there were two major foci of labeled cells: (1) the depths of the intraparietal sulcus including areas VIP, LIP, and PEa, and (2) the anterior wall and fundus of the superior temporal sulcus including areas PP and MST. Smaller numbers of labeled cells were found in superior temporal sulcal areas FST, MT, and STP, posterior cingulate area 23b, area 3a within the central sulcus, areas SII, RI, Tpt in the lateral sulcus, and parietal areas 7a, 7b, PEc, MIP, DP, and V3A. Many of these posterior afferent cortical areas code visual-motion (MT, MST, and FST) or visual-motion and vestibular (PP, VIP) signals, consistent with the responses of neurons in FEFsem and with the overall physiology and anatomy of the smooth-pursuit eye movement system.
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PMID:Cortical afferents to the smooth-pursuit region of the macaque monkey's frontal eye field. 1594 Apr 95


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