Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the case of a patient in whom we diagnosed two different thyroid carcinomas (one on each lobe) of distinct histologic type: one derived from the follicular cells (papillary) and one from the C cells (medullary). They were both diagnosed preoperatively by fine needle aspiration (FNA), and the diagnosis was confirmed with histologic examination. "Inappropriate" staining with neuroendocrine markers was observed in the papillary tumor. Analysis of tumor tissue for the RET oncogene mutations, commonly found in the MEN2 syndromes, was negative. This case supports the view of a common origin for these two tumor types.
Gen Diagn Pathol 1997 Jun
PMID:Simultaneous occurrence of a medullary and a papillary thyroid carcinoma in the same patient. 922 64

Effects of epidermal growth factor (EGF) and possible mechanisms of EGF-mediated signal transduction were investigated in isolated cells of the digestive gland of the mussel (Mytilus galloprovincialis Lam. ). EGF induced a cytosolic Ca2+ transient and subsequently stimulated DNA synthesis; both effects were dose-dependent in the nanomolar range and inhibited by pretreatment with an inhibitor of tyrosine kinase activity, suggesting specific EGFR-like receptors. The EGF-induced cytosolic Ca2+ transient was mainly due to a Ca2+ influx through the plasma membrane, possibly involving voltage-insensitive Ca2+ channels. Such a Ca2+ response was abolished by pretreatment with indomethacin and NDGA, inhibitors of arachidonic acid metabolism; similarly, the EGF-stimulated increase in DNA synthesis was significantly reduced. Indomethacin, a cyclooxygenase inhibitor, had the greatest effect on both EGF-induced responses. Results suggest the presence of EGF-responsive cells in the mussel digestive gland. A possible role for arachidonic acid and its metabolites in mediating the effects of EGF is also indicated.
Gen Comp Endocrinol 1997 Aug
PMID:Effects of epidermal growth factor on isolated digestive gland cells from mussels. 924 30

1. Electrophysiological studies have shown that a number of different types of potassium (K) channel currents exist in mammalian neurons. Among them are the voltage-gated K channel-currents which have been classified as fast-inactivating A-type currents (KA) and slowly inactivating delayed-rectifier type currents (KDR). 2. Two major molecular superfamilies of K channel have been identified; the KIR superfamily and the Shaker-related superfamily with a number of different pore-forming alpha-subunits in each superfamily. 3. Within the Shaker-related superfamily are the KV family, comprising of at least 18 different alpha-subunits that almost certainly underlie classically defined KA and KDR currents. However, the relationship between each of these cloned alpha-subunits and native voltage-gated K currents remains, for the most part, to be established. 4. Classical pharmacological blockers of voltage-gated K channels such as tetraethylammonium ions (TEA), 4-aminopyridine (4-AP), and certain toxins lack selectivity between different native channel currents and between different cloned K channel currents. 5. A number of other agents block neuronal voltage-gated K channels. All of these compounds are used primarily for other actions they possess. They include organic calcium (Ca) channel blockers, divalent and trivalent metal ions and certain calcium signalling agents such as caffeine. 6. A number of clinically active tricyclic compounds such as imipramine, amitriptyline, and chlorpromazine are also potent inhibitors of neuronal voltage-gated K channels. These compounds are weak bases and it appears that their uncharged form is required for activity. These compounds may provide a useful starting point for the rational design of novel selective K channel blocking agents.
Gen Pharmacol 1998 Jan
PMID:Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. 945 76

Transmission of zucchini yellow mosaic virus (ZYMV) by aphids was examined by introducing mutations within the highly conserved proline-threonine-lysine (PTK) motif of the helper component proteinase (HC-Pro) using a cDNA full-length clone. Replacement of proline by alanine (ATK) in the PTK motif abolished transmission almost completely both from plants and from membranes. Substitution of the basic lysine by glutamic acid (PTE) did not reduce the rate of transmission compared with the wild-type. Replacement of threonine by valine (PVK) or serine (PSK) resulted in a rate of transmission that was lower than that of the wild-type. The rate was lower for PSK than for PVK. Western blot comparison did not permit attribution of HC-Pro functionality in transmission to its level in the host. The HC-Pro of strains that effected transmission (with the wild-type PTK motif, and with the mutated PTE and PVK motifs) could also bind in vitro to virions of ZYMV. HC-Pro with a PSK motif, which was less effective in assisting transmission, could bind only weakly to virions, while HC-Pro of the almost non-transmissible strains (with PAK and ATK motifs) did not bind at all. Interestingly, positive binding was recorded for transmission-defective ZYMV-Ct, which has a PTK motif but has glutamic acid instead of lysine in the lysine-leucine-serine-cysteine (KLSC) motif. These findings support the 'bridge hypothesis', and confirm the binding of the HC-Pro to the virion. The possible role of the PTK and KLSC motifs in binding to the virus and to the mouthparts of the aphid is discussed.
J Gen Virol 1998 Apr
PMID:Mutations in the HC-Pro gene of zucchini yellow mosaic potyvirus: effects on aphid transmission and binding to purified virions. 956 86

Transcription of the genes for sulfur assimilation and methionine biosynthesis in Saccharomyces cerevisiae is regulated by the size of the intracellular pool of an organic sulfur compound. The identity of this compound is not clear, but suggestions include S-adenosylmethionine (SAM) and cysteine. By studying the repression of selected sulfur assimilation (MET) genes, we found that the ability to form cysteine from homocysteine is crucial for methionine-mediated repression to take place. The transcription of MET14 and MET25 could not be repressed by methionine in strains in which either STR4 (which encodes cystathionine beta-synthase) or STR1 (cystathionine gamma-lyase) was disrupted, whereas the repression was independent of GSH1 (which encodes the enzyme responsible for the first step in glutathione biosynthesis from cysteine). In contrast, cysteine could repress the MET genes in all of these strains. Two genes that presumably encode cystathionine gamma-synthase and cystathionine beta-lyase were identified by genetic disruption (ORFs YJR130c and YGL184c), yielding yeast strains that cannot convert cysteine into homocysteine. Repression by cysteine was possible in either disruptant, suggesting a role in repression for cysteine alone. While some repression of MET genes could be accomplished by homocysteine in a strain that cannot form SAM from methionine, a low intracellular level of SAM seems to be necessary for full cysteine-mediated repression to take place.
Mol Gen Genet 2000 Apr
PMID:Cysteine is essential for transcriptional regulation of the sulfur assimilation genes in Saccharomyces cerevisiae. 1082 Nov 89

Posttraumatic stress disorder (PTSD) is a prevalent disorder that adversely affects 2-5% of the general population. Little is known about PTSD in the primary care setting. The purpose of the present study was to evaluate the utility of a screening instrument for PTSD (the PCL-C) in primary care and to examine comorbidity, disability, and patterns of healthcare utilization among persons with PTSD in this setting. Adult, English-speaking patients attending for routine medical care (N=368) participated in a two-stage screening consisting of the administration of a self-report measure for posttraumatic stress disorder (the PCL-C) followed by a structured diagnostic interview. Current (1-month) prevalence of PTSD was determined, as were current comorbid disorders. Brief functional impairment and disability indices were administered, and healthcare utilization in the prior 6 months was ascertained. 11.8% (standard error 1.7%) of primary care attendees met diagnostic criteria for either full or partial PTSD. Comorbidity with major depression (61% of cases of PTSD) and generalized anxiety disorder (39%) was common, but less so with social phobia (17%) and panic disorder (6%). Substance use disorder comorbidity (22%) was also fairly common. Patients with PTSD reported significantly more functional impairment than patients without mental disorders. Patients with PTSD also made greater use of healthcare resources than not mentally ill patients. PTSD frequently is encountered in primary care, and is associated with considerable functional impairment and healthcare utilization. Comorbidity with other mood and anxiety disorders is extensive. It remains to be seen if greater awareness and more aggressive treatment of PTSD in primary care will lead to improved functioning and reduced (or more appropriate) healthcare utilization. These are topics for further study.
Gen Hosp Psychiatry
PMID:Posttraumatic stress disorder in the primary care medical setting. 1093 33

Plastids of higher plants operate with at least two distinct DNA-dependent RNA polymerases, which are encoded in the organelle (PEP) and in the nucleus (NEP), respectively. Plastid run-on assays and Northern analyses were employed to analyse gene expression in tobacco mutant plastids lacking the PEP genes rpoA, rpoB or rpoC1. Hybridisation of run-on transcripts to restriction fragments representing the entire tobacco plastid chromosome, as well as to selected plastid gene-specific probes, shows that all parts of the plastid DNA are transcribed in rpo-deficient plastids. In comparison to wild-type chloroplasts, which are characterized by preferential transcription of photosynthesis-related genes in the light, mutant plastids exhibit a different transcription pattern with less pronounced differences in the hybridisation intensities between the individual genes. The analysis of steady-state transcript patterns and transcription rates of selected genes in both types of plastids demonstrates that differences in transcription rates are not necessarily paralleled by corresponding changes in transcript levels. The accumulation of large transcripts in the mutant plastids indicates that processing of primary transcripts may be impaired in the absence of PEP. These data suggest that, contrary to the prevailing view, much of the regulation of NEP-driven plastid gene expression in the rpo-deficient mutants is not based on differential promoter usage but is exerted at post-transcriptional levels.
Mol Gen Genet 2000 Jul
PMID:Disruption of plastid-encoded RNA polymerase genes in tobacco: expression of only a distinct set of genes is not based on selective transcription of the plastid chromosome. 1095 88

The Dutch swine vesicular disease virus (SVDV) isolate NET/1/92 was one of the first isolates belonging to a new SVDV antigenic group. This strain was completely sequenced and was shown to have 93% similarity with the UKG/27/72 isolate. To enable antigenicity, replication, maturation and pathogenicity studies of NET/1/92, an infectious full-length cDNA clone, designated pSVD146, was prepared. The in vitro and in vivo biological properties of the virus derived from pSVD146 were studied by analysing antigenicity, plaque morphology, growth curves and virulence in pigs. The epitopes of newly prepared monoclonal antibodies were roughly mapped by fusion-PCR. Fine mapping of epitopes at the amino acid level was achieved by introducing single amino acid mutations in pSVD146. Two new amino acids important in epitope formation were located in VP1; one was mapped in the C-terminal end and the second is thought to be located in the H-I loop. Growth curve and plaque sizes in vitro were similar between virus derived from pSVD146 and the parent wild-type virus. In virulence studies in pigs, the lesions score, neutralization titres and the seroconversion rates were comparable between virus derived from pSVD146 and the parent strain. Since virus derived from pSVD146 had the same biological properties as the parent strain NET/1/92, the full-length infectious cDNA clone pSVD146 will be very useful in studies of the antigenicity, virulence, pathogenesis, maturation and replication of SVDV.
J Gen Virol 2000 Nov
PMID:Construction of a full-length infectious cDNA clone of swine vesicular disease virus strain NET/1/92 and analysis of new antigenic variants derived from it. 1103 90

Hyperactivation of Cdc2 in fission yeast causes cells to undergo a lethal premature mitosis, a phenomenon called mitotic catastrophe. This phenotype is observed in cdc2-3w wee1-50 cells at high temperature and is suppressed by a single recessive mutant, mcs3-12. Mcs3 acts independently of the Wee1 kinase and Cdc25 phosphatase, two major regulators of Cdc2. We have isolated multicopy suppressors of the cell cycle arrest phenotype of mcs3-12 wee1-50 cdc25-22 cells, but did not identify the mcs3 gene itself. Instead several known mitotic regulators were isolated, including the Cdc25 phosphatase, Wis2 cyclophilin, Cek1 kinase, and an Hsp90 homologue, Swo1. We also isolated clones encoding non-functional, truncated forms of the Wee1 kinase and Dis2 type 1 phosphatase. In addition we identified a multicopy suppressor that encodes a structural homologue of the budding yeast SPO12 gene. We find that overexpression of fission yeast spo12 not only suppresses the phenotype of the mcs3-12 wee1-50 cdc25-22 strain, but also that of a win1-1 wee1-50 cdc25-22 strain at high temperature, indicating that the function of spo12 is not directly related to mcs3. We show that spo12 mRNA is periodically expressed during the fission yeast cell cycle, peaking at the G2/M transition coincidently with cdc15. Deletion of spo12, however, has no overt effect on either the mitotic or meiotic cell cycles, except when the function of the major B type cyclin, Cdc13, is compromised.
Mol Gen Genet 2000 Oct
PMID:spo12 is a multicopy suppressor of mcs3 that is periodically expressed in fission yeast mitosis. 1108 71

Hwansodan has been used as a prescription for senile and vascular dementia in Oriental medicine. We investigated the neuroprotective effects of Hwansodan water extract on the apoptotic death of PC12 cells by serum deprivation. Hwansodan significantly rescued PC12 cells from apoptotic death by serum deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Hwansodan attenuated nuclear condensation and fragmentation, which represents typical neuronal apoptotic characteristics. Hwansodan also prevents DNA fragmentation and caspase-3-like protease activation in serum-deprived PC12 cells and induces the tyrosine phosphorylation of proteins around 44 kDa, which was identified as ERK1 with electrophoretic gel mobility shift by Western blot. In addition, MEK inhibitor PD98059 and Ras inactivator, alpha-hydroxyfarnesylphosphonic acid and mevastatin, attenuated the neuroprotective effects of Hwansodan in serum-deprived PC12 cells. These results indicate that Ras/MEK/ERK signaling pathway plays a role in neuroprotective effects of Hwansodan in serum-deprived PC12 cells.
Gen Pharmacol 2000 Apr
PMID:Hwansodan protects PC12 cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein (MAP) kinase pathway. 1128 16


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