Solitary fibrous tumour of the orbit.
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Adult↗
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Results for “DOMS”
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LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex.
Both the phenethylamine hallucinogen (-)-1-2, 5-dimethoxy-4-bromophenyl-2-aminopropane (DOB), a selective serotonin 5-HT2A,2C receptor agonist, and the indoleamine hallucinogen D-lysergic acid diethylamide (LSD, which binds to 5-HT1A, 1B, 1D, 1E, 1F, 2A, 2C, 5, 6, 7, dopamine D1 and D2, and alpha1 and alpha2 adrenergic receptors), but not their non-hallucinogenic congeners, inhibited N-methyl-D-aspartate (NMDA)-induced inward current and NMDA receptor-mediated synaptic responses evoked by electrical stimulation of the forceps minor in pyramidal cells of the prefrontal cortical slices. The inhibitory effect of hallucinogens was mimicked by 5-HT in the presence of selective 5-HT1A and 5-HT3 receptor antagonists. The inhibitory action of DOB, LSD and 5-HT on the NMDA transmission was blocked by the 5-HT2A receptor antagonists R-(+)-alpha-(2, 3-dimethoxyphenil)-1-[4-fluorophenylethyl]-4-piperidineme thanol (M100907) and ketanserin. However, at low concentrations, when both LSD and DOB by themselves only partially depressed the NMDA response, they blocked the inhibitory effect of 5-HT, suggesting a partial agonist action. Whereas N-(4-aminobutyl)-5-chloro-2-naphthalenesulphonamide (W-7, a calmodulin antagonist) and N-[2-[[[3-(4'-chlorophenyl)- 2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxy-b enzenesulphonamide phosphate (KN-93, a Ca2+/CaM-KII inhibitor), but not the negative control 2-[N-4'methoxybenzenesulphonyl]amino-N-(4'-chlorophenyl)-2-propeny l-N -methylbenzylamine phosphate (KN-92), blocked the inhibitory action of LSD and DOB, the selective protein kinase C inhibitor chelerythrine was without any effect. We conclude that phenethylamine and indoleamine hallucinogens may exert their hallucinogenic effect by interacting with 5-HT2A receptors via a Ca2+/CaM-KII-dependent signal transduction pathway as partial agonists and modulating the NMDA receptors-mediated sensory, perceptual, affective and cognitive processes.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
A case of a giant renal aneurysm.
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Abdominal Pain↗
Regulation of serotonin2A receptors in heterologous expression systems.
The serotonin2A and serotonin2C receptors are unique among receptors coupled to guanine nucleotide binding proteins in that chronic treatment in vivo with agonists as well as antagonists decreases receptor density. In an attempt to uncover molecular events involved in down-regulation of the serotonin2A receptor, the ability of agonists and antagonists to alter receptor density was examined in three heterologous expression systems, i.e., transfected NIH 3T3, transfected Madin-Darby canine kidney, and transfected AtT-20 cells. All three transfected cell lines exhibited pharmacological properties consistent with that predicted for cells expressing the serotonin2A receptor. However, the three cell lines displayed different receptor regulation properties in response to drugs acting at the serotonin2A receptor. In transfected NIH 3T3 cells, neither agonist nor antagonist treatment altered receptor density. Treatment with agonist as well as antagonist led to up-regulation of the serotonin2A receptor in transfected Madin-Darby canine kidney cells. In transfected AtT-20 cells, treatment with agonist led to receptor down-regulation, whereas antagonist treatment increased receptor density. Thus, the cellular background in which the serotonin2A receptor is expressed appears to determine the regulation properties of the receptor.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Effects of iron deprivation on Mycobacterium avium growth.
SETTING: Acquired immune deficiency syndrome (AIDS) patients have increased iron deposition in different tissues which may favour the growth of Mycobacterium avium, a common bacterial opportunist in these patients. OBJECTIVE: To test whether reducing the iron loads in macrophages in vitro and in vivo reduces M. avium proliferation. DESIGN: Mycobacterial proliferation was evaluated in vitro either in axenic media or cultured macrophages and in vivo in mice after manipulation of the iron status. RESULTS: Three different compounds--desferrioxamine (DFO), N,N'bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and a 1-amino-3-(2-bipyridyl)isoquinoline derivative (VUF8514)--were found to inhibit the growth of M. avium in axenic medium. DFO and HBED were also active in inhibiting the intramacrophagic growth of M. avium, while the use of VUF8514 was prevented by its toxicity towards the host cell. Both DFO and HBED enhanced the mycobacteriostatic effect induced in bone marrow derived macrophages by interferon gamma. In vivo, an iron poor diet led to reduced M. avium proliferation whereas the intraperitoneal administration of either DFO or HBED had small effects as they impacted little on the iron status of mice. CONCLUSION: These results confirm that iron withholding is a means of inhibiting the growth of M. avium. In vitro data suggest that iron chelating compounds may be useful as adjunct therapy against M. avium, once their in vivo activity is optimized.
Animals↗
[Explanation of an unclear neurological syndrome by toxicologic investigation].
HISTORY AND CLINICAL FINDINGS: A 51-year-old man without relevant previous illness developed vomiting and diarrhoea, later also tingling and hypaesthesias in the limbs, as well as optical hallucinations that had occurred after a mid-day meal and drinking red wine. Neurological examination revealed variable pupillary reactions with anisocoria that would change from one side to the other. There was no paresis, muscle reflexes were brisk, more so on the right. Babinski reflex was positive on the right, there was an unsustained clonus of the right foot and the coordination tests were normal. Distal symmetrical hypaesthesias and paraesthesias were present in all limbs. An exogenous psychosis with restlessness and optical hallucinations was observed. INVESTIGATIONS: Routine blood count revealed leukocytosis. Serum concentrations of cGt and GPT were raised. Cerebral computed tomography and cerebrospinal fluid as well as microbiological tests of the mid-day meal were normal. DIAGNOSIS, TREATMENT AND COURSE: As the cause of the symptoms was initially unclear the patient was admitted to hospital and monitored without any specific treatment. Within one night all symptoms had disappeared and he was discharged the next morning without any complaints. Later the red wine which he had drunk was examined toxicologically and found to contain the "designer drug" DOB (2,5-dimethoxy-4-bromamphetamine). CONCLUSION: Accidental poisoning with DOB is probably a rare event which can hardly be included in routine differential diagnosis. If an acute cerebral organic syndrome has been excluded, only toxicological investigation can help in establishing the diagnosis in such cases.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Stereochemical considerations of the actions of some psychotropic drugs.
Stereoisomers have been used as tools to investigate the role of spatial (3-dimensional) features in neurochemical and behavioral effects of psychotropic drugs. Studies using enantiomers (optical isomers), geometrical isomers and semi-rigid molecules have shown that spatial features play a role in effects of antidepressant, antipsychotic, antiparkinsonian, and antianxiety drugs, as well as stimulants and psychotomimetics. An understanding of the role of spatial features in effects of psychotropic drugs might aid in reducing their side effects and in enhancing their therapeutic efficacy.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Fetal akinesia sequence caused by nemaline myopathy.
Nine patients with the characteristic signs of fetal akinesia sequence (polyhydramnion, multiple joint contractures and lung hypoplasia) are described. In 8 of the 9 patients nemaline myopathy could be demonstrated with histology. The ninth patient presented the same phenotype as his 4 affected siblings in whom the nemaline myopathy could be histologically proven. Seven of the patients belonged to 2 families; the other 2 patients were isolated cases. In one fetal case nemaline myopathy was documented at week 22 of gestation. These observations demonstrate that nemaline myopathy can cause the fetal akinesia sequence, with onset of first symptoms as early as the beginning of the second trimester of pregnancy.
Abnormalities, Multiple↗
Diagnosis of atypical intracerebral Langerhans cell histiocytosis suggested by concomitant lung abnormalities. A case report.
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Adult↗
Variability of outcome in Joubert syndrome.
Two children with Joubert syndrome are reported. Patient one is the first case with Joubert syndrome where CT-findings are confirmed by autopsy. Until now only three cases with necropsy findings were reported. Patient two shows a remarkable clinical outcome not previously mentioned.
Cerebellum↗
Cervical ripening and induction of labor with misoprostol, dinoprostone gel, and a Foley catheter: a randomized trial of 3 techniques.
OBJECTIVE: The purpose of this study was to compare the efficacy of 3 different techniques of cervical ripening and induction. STUDY DESIGN: Patients who required cervical ripening and induction were randomized to one of 3 groups: (1) supracervical Foley catheter and intravaginal dinoprostone gel, (2) supracervical Foley catheter and 100 microg oral doses of misoprostol, or (3) serial 100-microg oral doses of misoprostol. Intravenous oxytocin was administered when a protraction disorder of labor was identified. RESULTS: There were 339 women randomized. There was no significant difference in the time from first intervention to delivery in the 3 groups (P =.546). In each group, a similar percentage of women required oxytocin (P =.103). The rates of cesarean delivery were equivalent among the groups (P =.722). Rates of tachysystole were high but statistically equivalent among the 3 groups. There were no significant differences in Apgar scores or umbilical artery pH. CONCLUSION: Oral 100 microg serial doses of misoprostol, with or without the use of a supracervical Foley catheter, were equivalent to the use of a supracervical Foley catheter and serial 4-mg doses of dinoprostone gel for cervical ripening and the induction of labor.
Adult↗
Radiographic manifestation of clear cell odontogenic tumor.
Clear cell odontogenic tumors are uncommon, only 20 cases having been reported in the literature. We report a case that presented with unique radiographic manifestations over a period of 12 years; no similar case has been reported to date. Documentation of the malignant nature of the condition and of the range of clinical and radiographic manifestations with which this neoplasm can present provides useful insight into its pathogenesis and progression. Early and timely recognition of the lesion, histopathologic examination, and aggressive interventional procedures are in order to successfully treat this condition and prevent a potentially fatal outcome.
Adult↗
Endoscopic mitral valve repair: feasible, reproducible, and durable.
OBJECTIVE: We sought to document the feasibility, safety, and effectiveness of performing mitral valve repair using a totally endoscopic approach. METHODS: Between February 1997 and October 1, 2001, 187 patients underwent totally endoscopic mitral valve repair at our institution. The mean age was 60.7 +/- 13.1 years, and 62% were male. Median preoperative functional class and degree of mitral regurgitation were II and 4, respectively. Data collection included an institutional protocol assessing procedure-related pain, cosmesis, and functional recovery. Statistical analysis included Kaplan-Meier and Cox regression methods. Mean follow-up was 19 +/- 15.2 months and was 100% complete. RESULTS: Associated atrial procedures were performed in 9.1% (n = 17) of the patients. Two patients required intraoperative conversion to sternotomy. Thoracoscopic re-evaluation for suspected bleeding (n = 19) was part of our aggressive postoperative management. One patient required sternotomy for control of bleeding. Hospital mortality included 1 (0.5%) patient and was not technology related. There were 1 early and 6 late reoperations, 4 of which were due to endocarditis. No risk factors for repair failure could be detected. Freedom from mitral valve reoperation at 4 years was 93.3% +/- 2.6%. The median degree of mitral regurgitation at follow-up was 0. Ninety-three percent of the patients were highly satisfied with either no or mild postoperative pain, and 98.4% believed they had an aesthetically pleasing scar. CONCLUSIONS: Totally endoscopic mitral valve repair can be done safely with excellent results and a high degree of patient satisfaction. It is now our exclusive approach for isolated atrioventricular valve disease.
Adult↗
DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans.
DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs), efficiently binds and transmits HIVs and simian immunodeficiency viruses to susceptible cells in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently been described. Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these viruses to both T cell lines and human peripheral blood mononuclear cells. Binding of virus to DC-SIGNR was dependent on carbohydrate recognition. Immunostaining with a DC-SIGNR-specific antiserum showed that DC-SIGNR was expressed on sinusoidal endothelial cells in the liver and on endothelial cells in lymph node sinuses and placental villi. The presence of this efficient virus attachment factor on multiple endothelial cell types indicates that DC-SIGNR could play a role in the vertical transmission of primate lentiviruses, in the enabling of HIV to traverse the capillary endothelium in some organs, and in the presentation of virus to CD4-positive cells in multiple locations including lymph nodes.
Amino Acid Sequence↗
HIV-1 gp120 and chemokines activate ion channels in primary macrophages through CCR5 and CXCR4 stimulation.
HIV type 1 (HIV-1) uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry into target cells. Here we show that the HIV-1 envelope gp120 (Env) activates multiple ionic signaling responses in primary human macrophages, which are important targets for HIV-1 in vivo. Env from both CCR5-dependent JRFL (R5) and CXCR4-dependent IIIB (X4) HIV-1 opened calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages. These signals were mediated by CCR5 and CXCR4 because macrophages lacking CCR5 failed to respond to JRFL and an inhibitor of CXCR4 blocked ion current activation by IIIB. MIP-1beta and SDF-1alpha, chemokine ligands for CCR5 and CXCR4, respectively, also activated K(Ca) and Cl(-) currents in macrophages, but nonselective cation channel activation was unique to gp120. Intracellular Ca(2+) levels were also elevated by gp120. The patterns of activation mediated by CCR5 and CXCR4 were qualitatively similar but quantitatively distinct, as R5 Env activated the K(Ca) current more frequently, elicited Cl(-) currents that were approximately 2-fold greater in amplitude, and elevated intracellular Ca(+2) to higher peak and steady-state levels. Env from R5 and X4 primary isolates evoked similar current responses as the corresponding prototype strains. Thus, the interaction of HIV-1 gp120 with CCR5 or CXCR4 evokes complex and distinct signaling responses in primary macrophages, and gp120-evoked signals differ from those activated by the coreceptors' chemokine ligands. Intracellular signaling responses of macrophages to HIV-1 may modulate postentry steps of infection and cell functions apart from infection.
Calcium↗
Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules.
Loss of the renal endosome-associated chloride channel, ClC-5, in Dent's disease and knockout (KO) mice strongly inhibits endocytosis of filtered proteins by kidney proximal tubular cells (PTC). The underlying mechanism remains unknown. We therefore tested whether this endocytic failure could primarily reflect a loss of reabsorption by the multiligand receptors, megalin, and cubilin, caused by a trafficking defect. Impaired protein endocytosis in PTC of ClC-5 KO mice was demonstrated by (i) a major decreased uptake of injected 125I-beta 2-microglobulin, but not of the fluid-phase tracer, FITC-dextran, (ii) reduced labeling of endosomes by injected peroxidase and for the endogenous megalin/cubilin ligands, vitamin D- and retinol-binding proteins, and (iii) urinary appearance of low-molecular-weight proteins and the selective cubilin ligand, transferrin. Contrasting with preserved mRNA levels, megalin and cubilin abundance was significantly decreased in kidney extracts of KO mice. Percoll gradients resolving early and late endosomes (Rab5a, Rab7), brush border (villin, aminopeptidase M), and a dense peak comprising lysosomes (acid hydrolases) showed a disappearance of the brush border component for megalin and cubilin in KO mice. Quantitative ultrastructural immunogold labeling confirmed the overall decrease of megalin and cubilin in PTC and their selective loss at the brush border. In contrast, total contents of the rate-limiting endocytic catalysts, Rab5a and Rab7, were unaffected. Thus, impaired protein endocytosis caused by invalidation of ClC-5 primarily reflects a trafficking defect of megalin and cubilin in PTC.
Absorption↗
A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 Env to chemokine receptors.
The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an appropriate coreceptor, which triggers structural changes in Env that lead to fusion between the viral and cellular membranes. The major HIV-1 coreceptors are the seven transmembrane domain chemokine receptors CCR5 and CXCR4. The type of coreceptor used by a virus strain is an important determinant of viral tropism and pathogenesis, and virus-receptor interactions can be therapeutic targets. However, Envs from many virus strains interact with CXCR4 and CCR5 with low affinity such that direct study of this important interaction is difficult if not impossible using standard cell-surface binding techniques. We have developed an approach that makes it possible to study ligand binding to membrane proteins, including Env-coreceptor interactions, using an optical biosensor. CCR5, CXCR4, and other membrane proteins were incorporated into retrovirus particles, which were purified and attached to the biosensor surface. Binding of conformationally sensitive antibodies as well as Env to these receptors was readily detected. The equilibrium dissociation constant for the interaction between an Env derived from the prototype HIV-1 strain IIIB for CXCR4 was approximately 500 nM, explaining the difficulty in measuring this interaction using standard equilibrium binding techniques. Retroviral pseudotypes represent easily produced, stable, homogenous structures that can be used to present a wide array of single and multiple membrane-spanning proteins in a native lipid environment for biosensor studies, thus avoiding the need for detergent solubilization, purification, and reconstitution. The approach should have general applicability and can be used to correlate Env-receptor binding constants to viral tropism and pathogenesis.
Animals↗