Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0031511 (pheochromocytoma)
14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions. In contrast to control mice, they failed to improve their performance from the first to the last session. Nevertheless, when later required to repeatedly learn the same discrimination over several days (repetitive testing), animals with ACC lesions no longer exhibited any learning deficit. The converse pattern of results was found in mice with PCC lesions. These animals performed much more poorly than control animals during the acquisition and first reversal of the discrimination, but displayed remarkable improvement over the subsequent four reversal sessions, gradually overcoming their initial impairment. However, when later submitted to repetitive testing, these animals again showed a substantial learning deficit. Neither ACC nor PCC cingulate lesions significantly affected the animals' retention capacities as measured by single test-trials over a 24-h interval. Yet, mice with PCC lesions were retarded in reversal learning after a long intersession interval (10 days), indicating that PCC, but not ACC, lesions did interfere with some long-term retention processes. These results imply that the ACC, as a part of the medial frontal cortex, may play a crucial role in temporally ordering a series of spatial responses, whereas the PCC seems to contribute to the formation and retention of each individual spatial response, probably by transmitting information from limbic structures such as the anterior thalamus and hippocampal formation to posterior neocortical association areas.
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PMID:Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice. 175 Oct 4

To clarify gene alterations in functional human adrenal tumors, we performed molecular analysis for p53 abnormalities in 23 cases with adrenal neoplasms. The immunohistochemical study with anti-p53 monoclonal antibody pAb1801 demonstrated that 10 of 23 (43.5%) cases overexpressed p53 protein in the tumor cells. Using a polymerase chain reaction-single strand conformation polymorphism study, 5 of 6 (83.3%) pheochromocytoma tissues (1 malignant and 5 benign) and 11 of 15 (73.3%) adrenocortical adenomas (2 with Cushing's syndrome and 13 with primary aldosteronism, all benign) showed an apparent electrophoretic mobility shift between the tumor and its paired adjacent normal adrenal tissue. Such differences were detected in exon 4 (12 cases), exon 5 (2 cases), and exon 7 (3 cases). The types of these mutations in exon 4 were a substitution from threonine (ACC) to isoleucine (ATC) at codon 102 in 5 cases, from glutamine (CAG) to histidine (CAC) at codon 104 in 1 case, from glycine (GGG) to alanine (CGG) at codon 117 in 1 case, from glutamate (GAG) to glutamine (CAG) at codon 68 in 1 case, and single base changes resulting in a premature stop codon at codon 100 in 2 cases. A 2-basepair deletion at codon 175 in exon 5 resulting in a frame shift was identified in 1 case. A single point mutation was identified, resulting in the substitution of glutamine (CAG) for arginine (CGG) at codon 248 of exon 7 in 1 case. A single basepair deletion at codon 249 resulted in a frame shift in 2 cases. There was 1 case with malignant pheochromocytoma that combined a single point mutation in exon 4 and a single base deletion in exon 7. Only 2 of 23 cases showed a loss of a normal allele encoding in the p53 gene. Northern blot analysis with 1.8-kilobase p53 cDNA revealed that p53 mRNA was overexpressed in 6 cases. Our results indicate that high frequencies of p53 gene mutation, especially in exon 4, exist in functional adrenal tumors. As p53 protein is a regulator of guanine nucleotide synthesis, the loss of normal inhibitory regulation by the p53 mutation would serve to increase the availability of GTP for the transduction of signals essential for increased cell growth and hormone expression in the adrenal tumors. These findings suggest that the p53 gene mutation may play a role in the tumorigenesis of benign and functional human adrenal tumors.
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PMID:Mutations of the p53 gene in human functional adrenal neoplasms. 810 38

Biotin has a profound effect on the metabolism of rhizobia. It is reported here that the activities of the biotin-dependent enzymes acetyl-coenzyme A carboxylase (ACC; EC 6.4.1.2) and propionyl-coenzyme A carboxylase (PCC; EC 6.4.1.3) are present in all species of the five genera comprising the Rhizobiaceae which were examined. Evidence is presented that the ACC and PCC activities detectable in Rhizobium etli extracts are catalysed by a single acyl-coenzyme A carboxylase. The enzyme from R. etli strain 12-53 was purified 478-fold and displayed its highest activity with propionyl-CoA as substrate, with apparent K(m) and V(max) values of 0.064 mM and 2885 nmol min(-1) (mg protein)(-1), respectively. The enzyme carboxylated acetyl-CoA and butyryl-CoA with apparent K(m) values of 0.392 and 0.144 mM, respectively, and V(max) values of 423 and 268 nmol min(-1) (mg protein)(-1), respectively. K(+), or Cs(+) markedly activated the enzyme, which was essentially inactive in their absence. Electrophoretic analysis indicated that the acyl-CoA carboxylase was composed of a 74 kDa biotin-containing alpha subunit and a 45 kDa biotin-free beta subunit, and gel chromatography indicated a total molecular mass of 620 000 Da. The strong kinetic preference of the enzyme for propionyl-CoA is consistent with its participation in an anaplerotic pathway utilizing this substrate.
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PMID:Biochemical characterization of a Rhizobium etli monovalent cation-stimulated acyl-coenzyme A carboxylase with a high substrate specificity constant for propionyl-coenzyme A. 1476 18

Allelic variants in the promoter region of the serotonin transporter (5-HTT) gene have been implicated in several psychiatric disorders and personality traits. In particular, two common alleles in a variable repeat sequence of the promoter region (SLC6A4) have been differentially associated with a display of abnormal levels of anxiety and affective illness in individuals carrying the "s" allele. The aim of this study was to compare the basal cerebral metabolic activity of non-psychiatric subjects in fronto-limbic structures to determine whether differences exist in basal metabolic activity within this functional polymorphism. PET scans with fluorine-18 fluorodeoxyglucose as radiotracer were performed in 71 non-psychiatric subjects previously screened for psychopathology and subsequently genotyped for SLC6A4; PET images were compared with SPM2 according to s/s (n = 27), s/l (n = 25), and l/l (n = 19) groups considering a significance threshold in a priori selected areas of P < 0.001 and an extent threshold > or =5 voxels. The analysis showed an effect of interest among the three genotype groups in right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left posterior cingulate gyrus (PCC). Comparison between l/l vs. s/s showed increased metabolism for l/l in left middle frontal gyrus and an increase for s/s in right ACC and left PCC. Comparison between s/s vs. s/l showed an increase for s/s in left PCC and right ACC. Increased basal metabolism in fronto-limbic structures for the s/s group may be conceived as an "overactive metabolic state" of these structures, possibly related to an increased susceptibility for developing an anxiety-depression spectrum disorder.
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PMID:Frontal and limbic metabolic differences in subjects selected according to genetic variation of the SLC6A4 gene polymorphism. 1585 Jul 37

Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC--disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC--disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo--disease progression in 2 patients; Carcinoid--stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET--disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.
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PMID:The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. 1672 80

Together with a detailed behavioral analysis, simultaneous measurement of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) permits a better elucidation of cortical pain processing. We applied painful electrical stimulation to 6 healthy subjects and acquired fMRI simultaneously with an EEG measurement. The subjects rated various stimulus properties and the individual affective state. Stimulus-correlated BOLD effects were found in the primary and secondary somatosensory areas (SI and SII), the operculum, the insula, the supplementary motor area (SMA proper), the cerebellum, and posterior parts of the anterior cingulate gyrus (ACC). Perceived pain intensity was positively correlated with activation in these areas. Higher unpleasantness rating was associated with suppression of activity in areas known to be involved in stimulus categorization and representation (ventral premotor cortex, PCC, parietal operculum, insula) and enhanced activation in areas initiating, propagating, and executing motor reactions (ACC, SMA proper, cerebellum, primary motor cortex). Concordant dipole localizations in SI and ACC were modeled. Using the dipole strength in SI, the network was restricted to SI. The BOLD signal change in ACC was positively correlated to the individual dipole strength of the source in ACC thus revealing a close relationship of BOLD signal and possibly underlying neuronal electrical activity in SI and the ACC. The BOLD signal change decreased in SI over time. Dipole strength of the ACC source decreased over the experiment and increased during the stimulation block suggesting sensitization and habituation effects in these areas.
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PMID:A simultaneous EEG-fMRI study of painful electric stimulation. 1717 35

Psychometric studies of risk perception have categorized personal risks into social and physical domains. To investigate whether and how the human brain differentiates social and physical risks, we scanned human adults using functional magnetic resonance imaging when they identified potential risks involved in social and physical behaviors. We found that the identification of risky behaviors in both domains induced increased activations in the anterior medial prefrontal cortex (MPFC, BA9/10)/ventral anterior cingulate (ACC) and posterior cingulate (PCC) relative to identification of safe behaviors. However, social risks induced stronger anterior MPFC activation whereas physical risks were associated with stronger ventral ACC activity. In addition, anterior MPFC activity was negatively correlated with the rating scores of the degree of social risk whereas PCC activity was positively correlated with the rating scores of the degree of physical risk. Relative to an autobiographical control task, the social risk identification task induced stronger sustained activity in the left supplementary motor area/dorsal ACC and increased transient activity in bilateral posterior insula. The physical risk identification task, however, resulted in stronger sustained activity in the right cuneus/precuneus and increased transient activation in bilateral amygdala. Our results indicate the existence of distinct neural mechanisms underlying social and physical risk identifications and provide neural bases for the psychometric categorization of risks into different domains.
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PMID:Parsing neural mechanisms of social and physical risk identifications. 1857 Feb 5

The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABA(B), benzodiazepine, and M(3) but lower NMDA and GABA(A) binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, alpha(2), 5-HT(1A), and D(1) but lowest GABA(A) densities. The MCC has lowest AMPA, kainate, alpha(2), and D(1) densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABA(A), GABA(B), and M(2) receptors. The PCC and RSC differ in the higher M(1) and alpha(1) but lower M(3) densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex.
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PMID:Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. 1903 99

Individuals with alexithymia are typically unable to identify, understand, or describe their own emotions. Patients with anorexia nervosa (AN) have been shown to have high levels of alexithymia, and the latter trait may play an important role over the course of AN. However, relatively little is known about the underlying neurobiological relationships between alexithymia and AN. The aim of this study was to investigate the relationship between alexithymia level and brain activation in patients with AN. Thirty female patients participated in this study. Alexithymia was measured using the 20-item Toronto Alexithymia Scale. Functional magnetic resonance imaging was used to identify the brain regions that display abnormal hemodynamic activity while patients with AN were engaged in an emotional decision-making task. There was significant activation in the amygdala during the task, but not in the posterior and anterior cingulate cortices (PCC, ACC). However, PCC and ACC activation did vary as a function of alexithymia level. These results suggest that alexithymia in AN patients is associated with a deficit in the cognitive evaluation of negative emotions concerning body image. Alexithymia might play a crucial role in the emotional processing impairments that are often observed in AN patients, and this trait might ultimately help to better account for the psychopathological mechanism that underlies AN.
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PMID:Neural correlates of alexithymia in response to emotional stimuli: a study of anorexia nervosa patients. 1940 May 51

Evaluative-feedback, occurring in our daily life, generally contains subjective appraisal of one's specific abilities and personality characteristics besides objective right-or-wrong information. Traditional psychological researches have proved it to be important in building up one's self-concept; however, the neural basis underlying its cognitive processing remains unclear. The present neuroimaging study revealed the mechanism of evaluative-feedback processing at the neural level. 19 healthy Chinese subjects participated in this experiment, and completed the time-estimation task to better their performance according to four types of feedback, namely positive evaluative- and performance-feedback as well as negative evaluative- and performance-feedback. Neuroimaging findings showed that evaluative- rather than performance-feedback can induce increased activities mainly distributed in the cortical midline structures (CMS), including medial prefrontal cortex (BA 8/9)/anterior cigulate cortex (ACC, BA 20), precuneus (BA 7/31) adjacent to posterior cingulate gyrus (PCC, BA 23) of both hemispheres, as well as right inferior lobule (BA 40). This phenomenon can provide evidence that evaluative-feedback may significantly elicit the self-related processing in our brain. In addition, our results also revealed that more brain areas, particularly some self-related neural substrates were activated by the positive evaluative-feedback, in comparative with the negative one. In sum, this study suggested that evaluative-feedback was closely correlated with the self-concept processing, which distinguished it from the performance-feedback.
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PMID:Evaluative-feedback stimuli selectively activate the self-related brain area: an fMRI study. 1973 7


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