Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A thermodilution method was developed for the determination of human leg blood flow. The method is based on bolus injection of an indicator distally into the femoral vein, at room temperature, and recording of the dilution curve in the same vessel at the level of the inguinal ligament. The blood flow was computed automatically with two thermistors and an integrator. 2. The leg blood flow determined by this method at rest and during exercise at work loads of 50, 100 and 150 W in six healthy subjects was found to agree closely with measurements by an intraarterial indicator-dilution technique. A linear relationship was found between leg blood flow and work. The reproducibility of the blood flow determinations, expressed as the coefficient of variation for a single determination, was 12.9 at rest and 5.3 or less during exercise. 3. The method was used in two patients with occlusive arterial disease of the leg. Extremely low leg blood flows were found in these patients when they were forced to interrupt the exercise by severe calf pain
Clin Sci Mol Med 1978 May
PMID:Determination of human leg blood flow: a thermodilution technique based on femoral venous bolus injection. 75 Jan 53

1. Twelve patients with symptomatic Paget's disease were studied before starting treatment with salmon calcitonin (12-5 mug) subcutaneously twice daily. Eleven of them were studied again after 3 months on this therapy. 2. Although pretreatment values for urinary total hydroxyproline excretion and cardiac output were considerably increased in some patients, there was no correlation between these two variables in the group as a whole. 3. Treatment resulted in a striking reduction in disease activity; the mean urinary hydroxyproline decreased 67%. 4. There was, however, no significant fall in cardiac output or change in oxygen transport during treatment. 5. Of the eight patients with bone pain who received treatment, five claimed complete pain relief.
Clin Sci Mol Med Suppl 1975 Jun
PMID:Effect of salmon calcitonin on cardiac output, oxygen transport and bone turnover in patients with Paget's disease. 105 85

Neuropeptides in dorsal root ganglia (DRG) have been implicated in the pathogenesis of pain and neurogenic inflammation in experimental and clinical arthritis. Recently we demonstrated increased levels of substance P (SP) and calcitonin gene-related peptide (CGRP) confined to innervating DRG in adjuvant-mediated monoarthritis. We have now investigated whether changes in peptide content are reflected in altered neuropeptide gene expression and the time course involved. Using in situ hybridization we found marked increases in expression of beta-preprotachykinin (PPT; 81 +/- 24% rise) and alpha-CGRP (44 +/- 6% rise) mRNAs in innervating (ipsilateral L5) DRG neurones only. These increases occurred at the onset of acute inflammation (8 h) and persisted until chronic arthritis developed after 14 days. There were no changes in the proportion of DRG neurones expressing PPT or CGRP mRNAs. Messenger RNA encoding vasoactive intestinal polypeptide (VIP) was not induced. These data suggest that increased synthesis of PPT and CGRP peptides in DRG may play a role in the pathogenesis both of adjuvant-mediated acute inflammation and chronic arthritis.
Brain Res Mol Brain Res 1992 Nov
PMID:Increased expression of preprotachykinin, calcitonin gene-related peptide, but not vasoactive intestinal peptide messenger RNA in dorsal root ganglia during the development of adjuvant monoarthritis in the rat. 128 Dec 53

The expression of the principal opioid peptide gene, preproenkephalin A, is exquisitely regulated by primary afferent inputs to the spinal and medullary dorsal horns. This regulated expression in response to neural synaptic activity has been referred to as trans-synaptic regulation. To define which DNA regions could mediate this trans-synaptic regulation, transgenic 'HEC' mice whose genomes include 193 bp of the human preproenkephalin A promoter fused to a chloramphenicol acetyltransferase (CAT) reporter gene were studied. Mice received unilateral electrical stimulation of the trigeminal ganglion or adjuvant injection into the hindpaw, stimuli known to regulate dorsal horn proenkephalin expression in vivo. CAT activity conferred by this promoter displayed trans-synaptic upregulation with both stimuli. Although the level of the upregulation was 2- to 3-fold higher than the change in the wild type gene, several features of this induction paralleled aspects of the behavior of the wild-type gene: the rapidity of responses to trigeminal ganglion stimulation, the stimulation intensity dependence of responses to trigeminal ganglion stimulation and the time course of upregulation noted following adjuvant injection. Regulatory proteins binding to this restricted promoter region are thus likely to mediate aspects of dorsal horn enkephalin regulation by pain and other somatic stimuli.
Brain Res Mol Brain Res 1992 Apr
PMID:Primary afferent stimulation acts through a 193 base pair promoter region to upregulate preproenkephalin expression in dorsal horn of transgenic mice. 131 94

Intramuscular hemangiomas are idiopathic lesions which are either tumoral or developmental in origin. A close association of abnormal blood vessels with nerve fibers is found and may suggest that nerves have a primary inciting role in the development of these lesions. In the current study, the number of nerve fibers in different zones around the tumors, as well as the type of neuropeptides present in these fibers, was quantitatively assessed by computer-assisted image analysis of immunohistochemical staining of histological slides. The number of nerve fibers as determined by positive staining by anti-protein S-100 antibodies was found to be elevated in the immediate vicinity of the abnormal blood vessels. The density of the nerve fibers rapidly declined with increasing distance from the hemangiomas, reaching normal values at distances of over 2 mm. Furthermore, hemangiomas contain a significantly higher number of calcitonin gene-related peptide (CGRP), substance P, and Met-enkephalin-positive fibers. The most significant rise in number is that of CGRP-positive fibers. This neuropeptide is a known mitogen, which could be responsible for the growth of the hemangiomatous blood vessels. Substance P is a nociceptive neurotransmitter and its presence can explain the pain which often accompanies even tiny intramuscular hemangiomas.
Exp Mol Pathol 1992 Jun
PMID:Neuropeptidergic innervation of intramuscular hemangiomas. 137 96

The expression of c-fos-like protein has been suggested to be a marker for neuronal activity in nociceptive processing. The immunohistochemical detection of this protein was used to determine if different visceral noxious stimuli induce distinct patterns in the rat spinal cord. We have developed a mechanical visceral pain model which is based on the acute distention of the duodenum yielding a quantifiable behavioral endpoint, writhing-like activity. One hour following either intraperitoneal injection of acetic acid or the distention of the duodenum via a chronically implanted balloon catheter, the animals were processed for the immunocytochemical detection of c-fos-like protein in the spinal cord. Characteristic patterns of c-fos-like immunoreactivity were observed following each type of stimulus that differed in spinal laminar and segmental distribution, number of neurons expressing fos-like immunoreactivity and staining intensity. The chemical noxious stimulus induced c-fos bilaterally in laminae I and X predominantly in the thoraco-lumbar region of the spinal cord. In contrast, the mechanical noxious stimulus induced a greater number and more intense neuronal c-fos-like protein expression in laminae I-VI, IX and X. These data provide further evidence that there is a differential nociceptive modulation in mechanical noxious visceral stimulation.
Brain Res Mol Brain Res 1991 Sep
PMID:Differential c-fos-like protein expression in mechanically versus chemically induced visceral nociception. 166 14

By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all beta-endorphin (beta-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.
J Steroid Biochem Mol Biol 1991
PMID:Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons. 168 65

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.
Cell Mol Neurobiol 1990 Sep
PMID:Pain and neurotransmitters. 170 58

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.
J Mol Neurosci 1991
PMID:Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply. 171 33

1. The working hypothesis that neuropeptide gene expression in a neuron is an indicator of that neuron's physiological activity is discussed. 2. Representative examples from the literature are presented to support the hypothesis. 3. Further, we discuss the regulation of expression of two opioid peptides, preproenkephalin and preprodynorphin, in laminae I and II of the spinal cord and in nucleus caudalis of the trigeminal nuclear complex, where they may play a role in pain modulation. 4. The expression of the opioid peptide genes can be induced by both painful and nonnoxious stimuli in neurons in time-dependent and sensory-specific fashions.
Cell Mol Neurobiol 1990 Mar
PMID:Neuropeptide gene expression and neural activity: assessing a working hypothesis in nucleus caudalis and dorsal horn neurons expressing preproenkephalin and preprodynorphin. 197 Jul 58


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