Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that interleukin-8 (IL-8) is secreted from the placental and decidual tissues and that IL-8 levels in the amniotic fluids are significantly elevated by chorioamnionitis or labor pain. The present study was aimed at defining the localization of IL-8 mRNA as well as IL-8 protein at the feto-maternal interface using in situ hybridization and immunohistochemical staining. Both IL-8 mRNA and protein were localized in cytotrophoblast, syncytiotrophoblast and Hofbauer cells of the placenta, decidual stromal cells, decidual lymphocytes and endometrial gland cells. IL-8 secretion from glandular cells has not previously been reported. In addition, we confirmed IL-8 mRNA expression and secretion of IL-8 by an endometrial cancer cell line (Ishikawa) using the reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods, respectively.
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PMID:Detection and localization of interleukin-8 mRNA and protein in human placenta and decidual tissues. 773 6

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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PMID:Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. 877 36

To determine which alpha 2-adrenergic receptor subtypes are present in primary afferent and sympathetic postganglionic neurons we have performed in situ hybridization and immunohistochemistry experiments on rat dorsal root and superior cervical ganglia. Reverse transcriptase polymerase chain reaction was used as a preliminary screen for the presence of mRNA encoding alpha 2-adrenergic subtypes in dorsal root and superior cervical ganglia; polymerase chain reaction primers amplified distinct regions of the rat alpha 2A-(RG20), alpha 2B-(RNG) and alpha 2C-(RG10) adrenergic receptor subtypes in mRNA extracted from lumbar dorsal root and superior cervical ganglia. To localize receptors to cell types in the ganglia, in situ hybridization was performed on cryosections of dorsal root and superior cervical ganglia with oligonucleotide probes designed to distinguish between mRNA encoding for alpha 2-adrenergic receptor subtypes. Immunohistochemistry was performed with a polyclonal antibody against the alpha 2A-adrenergic receptor subtype. Our results with reverse transcriptase polymerase chain reaction indicate that all three alpha 2-adrenergic receptor subtypes are expressed in dorsal root and superior cervical ganglia. Data from the in situ hybridization experiments indicated that the mRNA detected with the reverse transcriptase polymerase chain reaction was present in neuronal cell bodies, except for the mRNA encoding the alpha 2A-adrenergic receptor which was not detectable in dorsal root ganglia. The distribution of mRNA encoding alpha 2B- and alpha 2C-adrenergic receptor subtypes among dorsal root ganglion neurons and alpha 2A-, alpha 2B- and alpha 2C-adrenergic receptor subtypes among superior cervical ganglion neurons suggests that multiple adrenergic receptor subtypes are present in a single neuron. Neuronal cell bodies in both the dorsal root and superior cervical ganglion consistently demonstrated alpha 2A-adrenergic receptor-like immunoreactivity. The apparent co-expression of multiple alpha 2-adrenergic receptor subtypes in dorsal root and superior cervical ganglion neurons enables a single transmitter to produce a number of effects in the same neuron; which receptors are functionally active may vary with the presence of nerve injury, inflammation or other physiological and pathophysiological conditions.
Pain 1997 Jan
PMID:Alpha 2-adrenergic receptor subtypes in rat dorsal root and superior cervical ganglion neurons. 906 29

Oxathlin carboxanilide analogs (UC) and alpha APA, compounds recognized as nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI), were evaluated for activity against the human immunodeficiency virus (HIV-1) and drug-resistant variants. These NNRTIs are structurally diverse but potent inhibitors of HIV-1 with efficacy in the nanomolar to low micromolar concentrations. They interact at a specific site in the pain domain of the p66 subunit of RT. Treatment of HIV-1 infected cell cultures with UC compounds resulted in the selection of drug-resistant viruses bearing specific amino acid changes at 100, 101, 103, 106, and/or 181. Since Y181C and L1001 are the most commonly observed resistance-engendering mutations, RT enzymatic analysis was correlated with molecular modeling to glean information on the structural interactions between these NNRTIs and RT. Information derived from these studies will facilitate rational drug design and the selection of complementary anti-HIV drugs for combination therapy.
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PMID:Cross-resistance analysis and molecular modeling of nonnucleoside reverse transcriptase inhibitors targeting drug-resistance mutations in the reverse transcriptase of human immunodeficiency virus. 920 8

Distal symmetrical peripheral neuropathy is a common adverse experience in persons with HIV infection. This condition, which presents as a pain, numbness. burning and/or dysaethesia initially in the feet, is often multi-factorial in its origin. Nucleoside analogue reverse transcriptase inhibitors represent an important contributor to peripheral neuropathy. Specifically, around 10% of patients receiving stavudine or zalcitabine and 1 to 2% of didanosine recipients may have to discontinue therapy with these agents due to neuropathy. Prompt withdrawal of these therapies enables gradual resolution of signs and symptoms in most patients, although a period of symptom intensification may occur shortly after withdrawal. Risk factors for developing peripheral neuropathy during nucleoside analogue therapy include low CD4+ cell count (<100 cells/mm3), a prior history of an AIDS defining illness or neoplasm, a history of peripheral neuropathy, use of other neurotoxic agents including high alcohol (ethanol) consumption and nutritional deficiencies such as low serum hydroxocobalamin levels. Thus, patients at increased risk of peripheral neuropathy should potentially avoid the use of the neurotoxic nucleoside analogues or be more carefully monitored during therapy. Management of this problem includes patient education. prompt withdrawal of the likely causative agent (giving consideration not to leave the patient on a sub-optimal therapy regimen) and simple analgesia. with augmentation with tricyclic antidepressants or anticonvulsant agents when pain is severe. New agents that may assist in managing this condition include levacecarnine (acetyl-L-carnitine) and nerve growth factors such as recombinant human nerve growth factor.
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PMID:Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management. 988 91

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 microliters) and higher concentrations (3 x NS, 6 x NS, 12 x NS, 24 x NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.
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PMID:Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans. 1043 Jul 43

Desmoplastic small cell tumor (DSCT) is a high-grade malignant neoplasm that shows polyphenotypic differentiation. Its almost exclusive involvement of serosal surfaces (particularly peritoneum) has led to the consideration of a putative "mesothelioblast" as the cell of origin. Although an extraserosal case involving the brain (presumably arising from the dura) has been reported, to date no case primary in the bone or soft tissues has been documented. The authors describe a 34-year-old man who presented with a 3-year history of pain in the right hand and a recently noted mass in the hypothenar area. Open biopsy followed by wide en bloc excision in combination with index ray resection was performed. Subsequently, the patient underwent ipsilateral axillary lymph node dissection. Extensive radiologic workup at the time of presentation and 12 months later revealed no tumor in the chest or abdomen. The patient was treated with an HD-CAV chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide) and was free of tumor until 18 months later, at which time he developed multiple metastases in the lungs. Currently, he is alive with tumor and in poor condition. The histologic sections of the mass displayed the characteristic features of DSCT involving bone and soft tissue. Immunohistochemical stains showed positivity of the tumor cells for muscle marker (desmin), neuroendocrine markers (chromogranin, synaptophysin), and epithelial markers (keratins CAM5.2, AE1:AE3, epithelial membrane antigen). Chimeric transcripts were detected by reverse transcriptase-polymerase chain reaction, indicating the presence of EWS-WT1 gene fusion, which is characteristically associated with DSCT. Sequence analysis showed in-frame fusion of EWS exon 9 to WT1 exon 8--a variant not documented in any other case. This is a unique example of DSCT primary in bone and soft tissues, which raises interesting questions about the histogenesis of this tumor type and its relationship to other small round cell tumors. Although the "mesothelioblast" hypothesis as the origin of DSCTs is attractive, it does not account for the tumors that are located in the brain or, as in this patient, in the soft tissues and bone. In addition, this patient demonstrates a rare variant of EWS-WT1 gene fusion not described in DSCT involving serosal surfaces.
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PMID:Primary desmoplastic small cell tumor of soft tissues and bone of the hand. 1055 10

The expression of the kappa-opioid receptor on human peripheral blood cells (in rheumatoid arthritis cases and normal volunteers) was examined using reverse transcriptase polymerase chain reaction (RT-PCR), and the relationship between its expression and the inflammatory activity or chronic pain in patients with rheumatoid arthritis (RA) was determined. RT-PCR was performed on the peripheral blood cells obtained from 37 patients with RA and 13 healthy volunteers. kappa-Opioid receptor mRNA expression was exhibited on the blood cells of 37% of RA patients (14/ 37) and 54% of healthy volunteers (7/13) , and the levels of expression were lower in the RA patients than in the healthy volunteers. Regarding the relationship between the expression of kappa-opioid receptor mRNA and the symptoms in RA patients, it was noted that the expression of the receptor mRNA was significantly decreased in RA patients in whom erythrocyte sedimentation rate (ESR), Lansbury index, and visual analogue pain scores were high. The kappa-opioid receptor mRNA was expressed on four cell types, namely, T and B cells, macrophages, and natural killer (NK) cells in RA patients; however, it was expressed only on the T and B cells and macrophages (and not on NK cells) in the healthy volunteers. Our findings suggest that the levels of expression of kappa-opioid receptor mRNA were decreased in RA patients in comparison with those in healthy volunteers; and that they were significantly related to the inflammatory activity or chronic pain in the RA patients. The higher the mRNA expression level, the less severe the inflammatory changes of RA. The kappa-opioid receptor may thus play a role in the modulation of nociception and anti-inflammatory changes in chronic inflammatory disorders.
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PMID:Expression of kappa-opioid receptor mRNA in human peripheral blood lymphocytes and the relationship between its expression and the inflammatory changes in rheumatoid arthritis. 1077 87

Acetylcholine (ACh) produces pain when applied to human skin and excites cutaneous mechanoreceptors and nerve terminals. These effects are partially mediated by activation of muscarinic receptors. The expression of muscarinic receptor subtype M2 has been shown in sensory neurons of rat dorsal root ganglia using reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization and immunohistochemistry. The purpose of the present study was to determine whether these M2 receptors are targeted to the peripheral endings of sensory neurons in the rat skin. Double-staining histochemical procedures were employed using a specific antiserum to M2 receptors combined with either of the following neuronal markers: an antiserum to the neuropeptide substance P, an antiserum to the protein gene product 9.5, which is a marker for peripheral nerve fibres, and the histochemical marker of a subpopulation of unmyelinated C-fibre afferents, I-B4, the Bandeira simplicifolia-derived isolectin. The M2 receptor subtype was found on different populations of nerve fibres. In the nerve plexus at the epidermal-dermal junction, M2 receptors are mainly present on I-B4-positive axons but are absent on fibres with substance P immunoreactivity. Sweat glands receive M2-receptor-immunoreactive fibres that express neither I-B4 binding nor substance P immunoreactivity, whereas blood vessels of the deeper dermis are innervated by I-B4-positive nerve fibres that are immunoreactive for M2 receptors and substance P. In addition to axon profiles, keratinocytes and endothelial cells also exhibit M2 receptor immunoreactivity. The results show the presence of M2 receptors in neuronal and non-neuronal cells, suggesting multiple effects of acetylcholine in the skin.
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PMID:Immunohistochemical localization of muscarinic receptors (M2) in the rat skin. 1092 69

This study examined the contribution of nerve injury alone or nerve injury with signs of neuropathic pain to alteration of kappa opioid receptor (KOR) mRNA expression. Two groups of mice, both of them were subjected to unilateral transection of the inferior and superior caudal trunks at the S1spinal nerve, were compared with respect to KOR mRNA expression by reverse transcriptase-polymerase chain reaction. One group showed exclusive pain behavior (PB+) as mechanical allodynia, and the other group exhibited no enhanced sensitivity to innocuous mechanical stimulation to the tail (PB-). Expression of total KOR and variants B and C mRNA increased ipsilaterally in dorsal root ganglia (DRG) of PB+ mice, whereas KOR variant A mRNA was not detected in DRG. These results show that KOR mRNA expression differs between PB+ and PB- groups of mice after nerve injury, and suggest an association of KOR expression with mechanical allodynia.
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PMID:Association of kappa opioid receptor mRNA upregulation in dorsal root ganglia with mechanical allodynia in mice following nerve injury. 1098 32


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