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)

Although uterine leiomyomas represent one of the most common neoplasms in adult women, their pathogenesis remains poorly understood. A cDNA microarray analysis was performed to search for candidate genes expressed to a greater degree in leiomyoma compared with matched myometrium. A total of 15 candidate genes was obtained; neuron-specific protein PEP-19 (Purkinje cell protein 4; PCP 4) exhibited a striking difference in expression between leiomyoma and myometrium. Although PEP-19 expression has been reported exclusively in the central nervous system, the present study demonstrated that PEP-19 is also expressed in other human organs, including prostate, kidney and uterus. To clarify the role of PEP-19 in the pathogenesis of leiomyomas, PEP-19 expression was investigated for a series of human leiomyoma, as well as normal myometrium and leiomyosarcoma. PEP-19 mRNA and protein expression were much stronger in leiomyomas compared with normal myometrium, suggesting that PEP-19 might be involved in leiomyoma pathogenesis.
Mol Hum Reprod 2003 Nov
PMID:PEP-19 overexpression in human uterine leiomyoma. 1456 13

We describe a reconstitution syndrome of immune responses to Pneumocystis carinii pneumonia (PCP) in 2 HIV-infected individuals who received highly active antiretroviral therapy (HAART). Patient 1, who had been successfully treated for PCP 3 years before the initiation of HAART, developed cough and pulmonary shadows 6 weeks after the start of HAART. Patient 2 was introduced HAART immediately after completing the responsive treatment of PCP, and then showed dyspnea and diffuse pulmonary infiltrates 7 months later. Histologic findings of lung-tissue samples showed granulomatous tissue (patient 1) and organizing pneumonia with thickening of alveolar septa (patient 2), and immunohistochemical findings revealed both CD4 and CD8 cell subsets represented in the lesions. The tissue and bronchoalveolar lavage (BAL) specimens showed no organisms, but PCR methods with the BAL samples were positive for P. carinii DNA. It is hypothesized that these second respiratory episodes may have arisen as immune reconstitution syndrome in response to residual P. carinii antigen in the lung.
Res Commun Mol Pathol Pharmacol 2002
PMID:Reconstitution of immune responses to Pneumocystis carinii pneumonia in patients with HIV infection who receive highly active antiretroviral therapy. 1508 Apr 97

Phencyclidine (PCP) produces schizophrenia-like symptoms in normal humans. This suggests that the dysfunction of glutamatergic neurotransmission may play an important role in the pathology of schizophrenia. However, PCP also exerts its effect on the mesolimbic dopamine (DA) system and modulates DA function in the brain, the abnormality of which is proposed to be a main pathology of schizophrenia. Recently, glial cell-line derived neurotrophic factor (GDNF) has been shown to play a protective role for DA neurons against neurotoxic injuries and maintaining DA function in the brain. We hypothesized that subchronic PCP may alter the function of GDNF in the ventral midbrain, where DA cell bodies are localized. Male Wistar rats were injected intraperitoneally with PCP daily for 10 days at 5 or 10 mg/kg, and their brains were removed 24 h after the last injection. The expressions of GDNF and its receptor (GFRalpha-1 and c-ret) mRNAs in the substantia nigra compacta (SNC) and ventral tegmental area (VTA) were determined by non-radioactive in situ hybridization, and those of GDNF and c-ret mRNA were found to be increased after the PCP subchronic administration. No significant changes, however, were observed in the expressions of GFRalpha-1 and basic fibroblast growth factor. These results suggest that subchronic PCP may modulate the function of the GDNF system, which exerts a trophic action on DA neurons in the ventral midbrain.
Brain Res Mol Brain Res 2004 Apr 29
PMID:Alterations in the expressions of mRNA for GDNF and its receptors in the ventral midbrain of rats exposed to subchronic phencyclidine. 1509 89

TCHQ is a major carcinogenic metabolite of the widely used wood preservative PCP. Recently, we found that TCHQ was a promoter in a mouse skin carcinogenesis model. However, the mechanism is still not clear. In this study, we showed that overexpression of Bcl-2 effectively suppressed TCHQ-induced apoptosis in NIH3T3 cells, as evidenced by morphological changes and DNA fragmentation. Although production of ROS contributes to TCHQ-induced apoptosis, Bcl-2 failed to attenuate TCHQ-elicited increase of intracellular ROS level. In addition, overexpressed Bcl-2 provides only partial protection against TCHQ-induced cellular DNA damage. We also found that TCHQ induced a change in mitochondrial transmembrane potential, and that caspase-9 and subsequent caspase-3 can be activated during TCHQ-induced acute apoptosis. Interestingly, TCHQ induced a significant upregulation of Bcl-2 expression, and over-expressed Bcl-2 can dramatically inhibit the change of mitochondria membrane potential and activation of both caspase-9 and -3. Thus, our results suggest TCHQ-induced tumor promotion may be through a mechanism of upregulation of Bcl-2 protein and subsequent apoptosis inhibition.
Mol Carcinog 2004 May
PMID:Bcl-2 overexpression inhibits tetrachlorohydroquinone-induced apoptosis in NIH3T3 cells: a possible mechanism for tumor promotion. 1510 27

1. Tetraponerines are a group of alkaloids occurring in the venoms of ants belonging to the genus Tetraponera. Eight compounds had been isolated and their structures elucidated, but their mechanisms of action had not yet been reported. We have studied the actions of several of these tetraponerines on vertebrate neuromuscular, ganglionic, and brain nicotinic acetylcholine receptors (nAChRs) using a variety of techniques including muscle contracture, cultured cell functional assays, neuronal patch clamping, and radioligand binding methods. 2. Potency for inhibition of the frog muscle carbachol-elicited contracture increased as the carbon 9 side chain alkyl group was increased in length to 10-12 carbons, then decreased when the chain was 18-carbons long. Potency differences between T-7 and T-8, which differ only in the stereochemistry of the carbon pentyl side chain were rather small. Quaternization of either N atom in a T-8 analog bearing a 10-carbon length alkyl substituent did not greatly affect potency for inhibition of the muscle response; thus the ionized form is an active form of this tetraponerine. 3. T-7 inhibited the nicotine-stimulated efflux of 86Rb from cultured PC12 cells, which primarily express alpha3-beta4 ganglionic type nicotinic receptors. T-8 blockade of BTX-sensitive and insensitive neuronal nAChRs, as studied by patchclamp recordings from cultured rat brain neurons, was also consistent with a noncompetitive type of inhibition. 4. T-7 displaced binding of the nAChR ion channel binding ligand thienylcyclophenidyl (TCP), an analog of PCP, to Torpedo neuromuscular type receptors. The affinity of the TCP binding site for T-7 did not depend upon the desensitization state of the receptor. 5. We conclude that the tetraponerines act at a site on nAChRs different from the ACh binding site which is probably located within the ion channel.
Cell Mol Neurobiol 2004 Aug
PMID:Nicotinic receptor inhibition by Tetraponera ant alkaloids. 1523 77

Recombinant p64, p65, p24, p22, p21 of the beet yellows closterovirus and pcp, hel, mtr, and pol fragments encoded by the replication genes of the virus were purified and tested for RNA binding. North-Western blotting revealed the RNA-binding activity for p64 and hel a 21-kDa fragment of the helicase domain with conserved motifs V and VI. Gel retardation assay confirmed hel binding with a randomized RNA probe in vitro, and a cooperative RNA-hel interaction was assumed on evidence of the binding pattern. The RNA-hel complexes proved to be stable at a high ionic strength.
Mol Biol (Mosk)
PMID:[RNA-binding properties of proteins of the beet yellows closterovirus]. 1528 26

Exuberant inflammatory responses are associated with respiratory failure during Pneumocystis pneumonia. Alveolar epithelial cells (AECs) promote Pneumocystis attachment and proliferation, but also contribute prominently to host cytokine-mediated inflammation during pneumonia. Recent investigations indicate that AECs produce macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-alpha (TNF-alpha) following challenge with Pneumocystis carinii. Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor critical for regulation of proinflammatory cytokine expression. Herein, we assess rat AEC NF-kappaB responses to challenge with a P. carinii beta-glucan cell wall component (PCBG). Prominent nuclear translocation of p65 NF-kappaB was demonstrated following PCBG challenge. NF-kappaB activation was in part mediated through Protein Kinase C (PKC) signaling pathways. PCBG challenge of AECs was also shown to induce MIP-2 and TNF-alpha mRNA production, a response that was ameliorated by NF-kappaB inhibition. MIP-2 protein expression was also dramatically increased by PCBG challenge, in a manner that was significantly attenuated by both PKC and NF-kappaB inhibition. The data further demonstrate that AEC chemokine responses were not mediated by the recently described dectin-1 receptor, but instead involved participation of cell surface lactosylceramide. These data support a significant role for AECs in host responses during Pneumocystis pneumonia, and further indicate that beta-glucan induces inflammatory cytokine production through NF-kappaB-dependent mechanisms.
Am J Respir Cell Mol Biol 2005 Jun
PMID:Pneumocystis cell wall beta-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-kappaB-dependent mechanisms. 1574 33

Both phencyclidine (PCP) and methamphetamine (MAP) can cause schizophrenia-like symptoms. To identify the molecules relating to the drug-induced psychotic state, we used serial analysis of gene expression in rodent cerebral cortices isolated 1 h after intraperitoneal injection of saline, PCP (10 mg/kg), or MAP (4 mg/kg). We analyzed a total of 150,000 tags and found significantly up- or down-regulated genes. The number of MAP-, PCP-, and MAP and PCP-reactive tags were 229, 215, and 41, respectively.
Brain Res Mol Brain Res 2005 Oct 31
PMID:Gene expression profiling in whole cerebral cortices of phencyclidine- or methamphetamine-treated rats. 1612 33

Dopaminergic dysfunction in the prefrontal cortex (PFC) has been implicated in the pathophysiology of schizophrenia. On the other hand, administration of the NMDAR antagonist phencyclidine (PCP) impairs PFC functions and induces a broad range of schizophrenic-like symptoms, thus has been widely used as an animal model for schizophrenia. This study sought to determine the mechanism by which PCP may alter the dopaminergic functions in PFC. In control rats, activation of dopamine D4 receptors produced a significant suppression of NMDA receptor transmission in PFC pyramidal neurons, which was dependent on the inhibition of active CaMKII. However, in PCP-treated rats, the D4 modulation of NMDA receptors was significantly impaired, with the concomitant loss of D4 regulation of CaMKII activity. In contrast, the D4 modulation of voltage-dependent Ca2+ channels was intact following PCP administration. Furthermore, treatment with the antipsychotic drug clozapine restored the D4 regulation of NMDA receptors in PCP-treated rats. These findings suggest that the selective disruption of the interaction between D4 and NMDA receptors in the PCP model, which is attributable to the impaired D4-mediated downstream signaling, may contribute to the aberrant PFC neuronal activity in schizophrenia.
Mol Cell Neurosci 2006 Jan
PMID:Aberrant regulation of NMDA receptors by dopamine D4 signaling in rats after phencyclidine exposure. 1619 23

To further determine the role of surfactant protein (SP)-D in the pathogenesis of Pneumocystis pneumonia, a mouse model of transgenic overexpression (OE) of SP-D was studied. These animals produce roughly 30- to 50-fold greater SP-D than their wild-type (WT) counterparts but show no other differences in lung morphology and function. Animals in both the SP-D OE and WT groups were depleted of CD4 lymphocytes with weekly injections of GK1.5 antibody, before Pneumocystis inoculation, and throughout the subsequent infection period. At various time points, mice were killed and analyzed for inflammatory parameters and organism burden. Proinflammatory cytokines in bronchoalveolar lavage fluid were elevated throughout the period of infection, with OE animals exhibiting significantly higher levels of TNF-alpha and macrophage inflammatory protein-2 compared with WT controls. The total number of cells in the lavage fluid was also increased significantly only in the OE group, whereas the cell differential composition demonstrated lymphocyte and eosinophil infiltration in both groups of animals. Significantly, the organism burden was markedly higher in the SP-D OE animals, whereas the WT mice demonstrated little alteration in organism number over the course of infection. These results further indicate that SP-D facilitates the development of Pneumocystis infection and related lung inflammation in an immunosuppressed mouse model.
Am J Physiol Lung Cell Mol Physiol 2006 Mar
PMID:Surfactant protein D enhances Pneumocystis infection in immune-suppressed mice. 1619 36


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