Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histological appearance of the gingiva in children with Down's syndrome (DS) was studied with special reference to inflammatory involvement and innervation. A dense infiltration of inflammatory cells was seen in the propria of most of the DS patients, including a few polymorphonuclear leucocytes. A hyperplasia of the epithelium was also found. The innervation of the gingiva was studied using immunohistochemistry. Nerve fibers as well as nerve bundles immunoreactive to neurofilament (NF) were seen in the propria, while occasionally intraepithelial NF fibers were observed. Calcitonin gene-related peptide (CGRP)-immunoreactive fibers and fiber bundles were also visualized, but they were less abundant than NF fibers. The density of NF and CGRP fibers and fiber bundles was estimated by semiquantitative evaluation. A higher density of NF and CGRP immunoreactive structures was observed in the propria of DS patients compared to the control subjects, while no obvious alteration was seen in their distribution in the propria. In addition, sparsely distributed fibers immunoreactive to peptide histidine isoleucine amide (PHI) and vasoactive intestinal polypeptide (VIP) fibers as well as neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were seen, mainly surrounding blood vessels. A few substance P (SP) fibers were also found, mostly close to the epithelium. No obvious differences of these sparsely distributed fibers were seen in the DS patients compared to controls. Thus, a profound inflammatory involvement of the gingiva of DS patients is seen concomitant with a hyperinnervation of the presumed sensory component of the gingival innervation. In contrast, no alterations were seen in the density of neuronal markers related to autonomic nerve fibers. The sensory hyperinnervation observed is probably not specifically related to DS, but may be due to a sprouting of afferent nerves induced by the inflammatory reaction. However, factors released from the sensory afferents could contribute to the gingival inflammation seen in DS.
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PMID:Immunohistological study of neuronal markers in inflamed gingiva obtained from children with Down's syndrome. 183 31

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
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PMID:Senile dementia of the Alzheimer type. 613 75

Neurochemical and histochemical techniques for characterization of neurotransmitters and their receptors in normal and pathological human brain have modified our understanding of Alzheimer's disease. From a hopeless clinico-pathological entity, it has become one of the models of possible physiopathological relations between neurotransmitter anomalies and dementia processes. Three types of neuromediator (or neuro-modulator): cholinergic, aminergic and peptidergic, appear to be affected to different degrees in 5 electively involved anatomical systems: cholinergic innominocorticoamygdalian and septohippocampic systems, noradrenergic ceruleocortical system, serotoninergic pontocortical system and cortical somatostatin and substance P systems. Critical analysis of neurochemical data shows that the biochemical nosology of Alzheimer's disease is confronted by the difficulty of constituting homogeneous series of both normal and pathological cases. Difficulties are increased when an attempt is made to establish correlations between neurotransmitter deficits and lesions or the demential process. This is the result of several factors: individual variability, difficulty in selecting valid controls, time elapsed before post-mortem sampling, imperfect understanding of the progressive topographical course of both cortical and subcortical lesions, which only now are being studied systematically and in a quantifiable manner, and finally the frequent absence of distinction between early and late forms of the disease. Truly senile forms should probably be distinguished, some authors believing them to be a particular type of aging process, from the presenile forms with more extensive biochemical changes. The constant presence of cholinergic symptoms show these to be fundamental features of the dementia but lesions of noradrenergic and serotoninergic systems also probably play an important role, and this triad is found in other dementia processes: trisomy 21, Parkinson's disease with dementia. Numerous questions concerning the neurotransmitter disorders in Alzheimer's disease remain unanswered: to what extent are the lesions due to neurone destruction? What occurs to the receptors? What factors condition severity of the disease? May the latter be directly correlated with the severity of the global dementia process or rather with the constitutive elements of the syndrome such as memory or attention disorders? What are the consequences of the peptidergic lesions? What is the sequential relation between lesions of corticopetal and intracortical afferent systems and what are their respective physiopathological significance?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Neurotransmitter anomalies in Alzheimer's disease]. 615 May 45

Amyloid beta peptides (AbetaP) deposit as plaques in vascular and parenchymal areas of Alzheimer's disease (AD) tissues and Down's syndrome patients. Although neuronal toxicity is a feature of late stages of AD, vascular pathology appears to be a feature of all stages of AD. Globular and nonfibrillar AbetaPs are continuously released during normal cellular metabolism, form calcium-permeable channels, and alter cellular calcium level. We used atomic force microscopy, laser confocal microscopy, and calcium imaging to examine the real-time and acute effects of fresh and globular AbetaP(1-42), AbetaP(1-40), and AbetaP(25-35) on cultured endothelial cells. AbetaPs induced morphological changes that were observed within minutes after AbetaP treatment and led to eventual cellular degeneration. Cellular morphological changes were most sensitive to AbetaP(1-42). AbetaP(1-42)-induced morphological changes were observed at nanomolar concentrations and were accompanied by an elevated cellular calcium level. Morphological changes were prevented by anti-AbetaP antibody, AbetaP-channel antagonist zinc, and the removal of extracellular calcium, but not by tachykinin neuropeptide, voltage-sensitive calcium channel blocker cadmium, or antioxidants DTT and Trolox. Thus, nanomolar fresh and globular AbetaP(1-42) induces rapid cellular degeneration by elevating intracellular calcium, most likely via calcium-permeable AbetaP channels and not by its interaction with membrane receptors or by activating oxidative pathways. Such rapid degeneration also suggests that the plaques, and especially fibrillar AbetaPs, may not have a direct causative role in AD pathogenic cascades.
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PMID:Fresh and globular amyloid beta protein (1-42) induces rapid cellular degeneration: evidence for AbetaP channel-mediated cellular toxicity. 1083 45

There has been little exploration of major biologic regulators of cerebral development in autism. In archived neonatal blood of children with autistic spectrum disorders (n = 69), mental retardation without autism (n = 60), or cerebral palsy (CP, n = 63) and of control children (n = 54), we used recycling immunoaffinity chromatography to measure the neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), and the neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4/5 (NT4/5). Neonatal concentrations of VIP, CGRP, BDNF, and NT4/5 were higher (ANOVA, all p values < 0.0001 by Scheffe test for pairwise differences) in children in the autistic spectrum and in those with mental retardation without autism than in control children. In 99% of children with autism and 97% with mental retardation, levels of at least one of these substances exceeded those of all control children. Concentrations were similar in subgroups of the autistic spectrum (core syndrome with or without mental retardation, other autistic spectrum disorders with or without mental retardation) and in the presence or absence of a history of regression. Among children with mental retardation, concentrations did not differ by severity or known cause (n = 11, including 4 with Down syndrome). Concentrations of measured substances were similar in children with CP as compared with control subjects. SP, PACAP, NGF, and NT3 were not different by diagnostic group. No measured analyte distinguished children with autism from children with mental retardation alone. In autism and in a heterogeneous group of disorders of cognitive function, overexpression of certain neuropeptides and neurotrophins was observed in peripheral blood drawn in the first days of life.
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PMID:Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation. 1135 50

Thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), substance P immuno-reactivity and choline acetyltransferase activity (CAT) were measured in post-mortem brains from 6 cases of Alzheimer-type dementia (ATD), 3 cases of Down's syndrome and 6 controls and in spinal cords from two cases of ATD and two controls. The activity of CAT was lower in posterior and anterior grey matter of lumbar spinal cord from two cases of ATD than from two controls. No significant differences were observed in the levels of the 3 peptides in the ATD, Down's and control brains and spinal cords, even in areas of ATD and Down's brain in which there were significant reductions in the activity of CAT or concentration of noradrenaline. These results show that TRH, LH-RH and substance P are not affected in ATD and Down's syndrome either as a consequence of a direct effect on the peptidergic neurone or of a secondary effect related to the loss of CAT activity and noradrenaline.
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PMID:Thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and substance P immuno-reactivity in post-mortem brain from cases of Alzheimer-type dementia and Down's syndrome. 2401 Jan 62