Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 54 y.o. woman presented with acute Coombs-negative hemolytic anemia at an outside hospital where she received 25 RBC transfusions and did not respond to prednisone or splenectomy. On transfer to our hospital, routine DAT and IAT were weakly positive, occasionally negative. When a modified "cold" antiglobulin test was employed, the result was strongly positive for IgG, weakly positive for C3d. Cold agglutinin titer was 32, and the Donath-Landsteiner test was negative. The autoantibody exhibited Pra specificity. The patient failed IV-IgG, high dose IV pulse steroids and cyclophosphamide, and continued to require daily transfusions. She responded 21 days after receiving daily plasma exchange (x3), with pulse cyclophosphamide on the third day, followed by escalating daily oral cyclophosphamide.
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PMID:Refractory immune hemolytic anemia with a high thermal amplitude, low affinity IgG anti-Pra cold autoantibody. 161 12

To evaluate the applicability of a radioactive 125I-anti-IgG test (RIAT) for the detection of small amounts of IgG antibodies on red blood cells (RBC) of patients with autoimmune hemolytic anemia of warm type (AIHA), RBC of 125 patients were studied (AIHA, n = 53; Coombs'-negative AIHA, n = 6; chronic cold agglutinin disease, n = 7; non-immune anemias, n = 59). It was found that the RBC of all cases (33/33) with a positive direct IgG antiglobulin test (DAT-IgG), but also 13 out of 20 patients with a negative DAT-IgG, but detectable complement (C3/C4), and 4 out of 6 cases with Coombs'-negative AIHA gave positive results in the direct RIAT. RBC-associated IgG was higher in the DAT-IgG positive group (n = 33; -x = 8.1%) than in the DAT-IgG negative group (n = 26; -x3.4%). There was no correlation between hypergammaglobulinemia and RBC-associated IgG. The sensitivity of the indirect RIAT was not remarkable better as compared to the indirect antiglobulin test. The RIAT is valuable in the serology of borderline cases of AIHA.
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PMID:Assessment of red cell autoantibodies in autoimmune hemolytic anemia of warm type by a radioactive anti-IgG test. 733 76

Autoimmuine hemolytic anemias (AIHA) are classified into two groups of warm type and cold type according to the thermal properties of the anti-red cell autoantibody. A positive result of the antiglobulin test (DAT) confirms the presence of autoantibodies on red cells. DAT-negative AIHA are diagnosed by means of the elevation of red blood cell-associated IgG. The sera in low titer cold agglutinin disease show a low cold agglutinin titer but a high titer in the presence of bovine albumin. The antigenic specificity of warm reacting autoantibodies has been demonstrated, by using immunoblot and immunoprecipitation, such as Rh-related proteins, band 3, glycophorin A or Wrb antigen.
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PMID:[Detection and characterization of anti-red cell autoantibodies in autoimmune hemolytic anemias]. 889 May 74

We studied 97 samples of patients being positive in the autocontrol of the indirect antiglobulin test (IAT) in the gel system (DiaMed). In 83.2%, retesting with monospecific anti-IgG serum gave also positive results, due to a specific phenomenon caused, for example, by drug-specific antibodies (AB), warm auto-AB or allo-AB. In contrast, only 52.9% of the samples retested by the standard tube technique with polyspecific antiglobulin serum reacted positive. Only in 6 patients slightly increased cold agglutinins could be detected. None of the investigated patients showed any clinical or laboratory signs of hemolysis except one with pernicious anemia. We conclude that positive results of the autocontrol in the gel IAT should be confirmed by an additional DAT in the tube technique. If this second test shows a negative result, transfusions can take place without any restrictions.
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PMID:[Value of positive auto controls in the gel centrifugation method]. 948 74

This study examined the concept of seating discomfort in a population of full-time wheelchair users with intact sensation. The goal was to construct a tool that would quantify seating discomfort experienced by wheelchair users. Ten participants were interviewed using ethnographic interview techniques. Data were analyzed using a cross-classifying matrix to examine commonalities among the 10 participants' responses. There were 16 discomfort and 13 comfort descriptors used by the participants. Of these, eight discomfort and five comfort descriptors were selected to include in the Wheelchair Seating Discomfort Assessment Tool (WcS-DAT). The discomfort descriptors selected were: aches and pains, need to move, pressure points, feeling poorly positioned, unable to concentrate, instability, not comfortable, and feeling too hot, cold or damp. The comfort descriptors selected were: absence of discomfort, feeling good, having no pain, able to concentrate, and feeling stable. The WcS-DAT also includes general information, such as the amount of time spent sitting and whether the individual was transferred into the chair properly--factors thought to affect discomfort--and ratings of discomfort intensity--in general and differentiated by body area. The WcS-DAT is a comprehensive tool for quantification of wheelchair seat discomfort for this population.
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PMID:Development of a consumer-driven Wheelchair Seating Discomfort Assessment Tool (WcS-DAT). 1509 77

A new serotonin transporter (SERT) ligand, [11C]2-[2-(dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [11C]AFA), was synthesized and evaluated as a candidate PET radioligand in pharmacological and pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either C-11 or F-18. In vitro, AFA displayed high affinity for SERT (Ki 1.46 +/- 0.15 nM) and lower affinity for norepinephrine transporter (NET, Ki 141.7 +/- 47.4 nM) or dopamine transporter (DAT, Ki > 10,000 nM). [11C]AFA (10) was prepared from its monomethylamino precursor 9 by reaction with high specific activity [11C]methyl iodide. Radiochemical yield was 43 +/- 20% based on [11C]methyl iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 +/- 1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats indicated that [11C]AFA accumulated in brain regions known to contain high concentrations of SERT. Binding in SERT-rich brain regions was reduced significantly by pretreatment with either the cold compound 8 or with the selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in vivo binding selectivity and specificity for SERT. Imaging experiments in baboons demonstrated that the uptake pattern of [11C]AFA in the baboon brain is consistent with the known distribution of SERT, with highest activity levels in the midbrain and thalamus, followed by striatum, hippocampus, and cortical regions. Activity levels in the baboon brain peaked at 15-40 min after radioligand injection, indicating a fast uptake kinetics for [11C]AFA. Pretreatment of the baboon with citalopram (4 mg/kg) significantly reduced the specific binding of [11C]AFA in all SERT-containing brain regions. Kinetic analysis revealed that the regional equilibrium specific to non-specific partition coefficients (V3") of [11C]AFA are similar to those of [11C]McN5652, but lower than those of [11C]AFM or [11C]DASB. In summary, [11C]AFA appears to be an appropriate PET radioligand with a fast brain uptake kinetics:
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PMID:A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [11C]2-[2-dimethylaminomethylphenylthio)]-5-fluorophenylamine ([11C]AFA). 1524 63

The diagnosis of mixed-type autoimmune haemolytic anaemia (AIHA) is based on demonstrating the presence of "warm" IgG auto-antibody and "low titre" ( < 64 at 4 degrees C), "high thermal amplitude" (reacting at or >30 degrees C) "cold" IgM auto-antibody. Mixed-type AIHA is uncommon. Red cell agglutination on the peripheral blood film is a common finding in mixed-type AIHA and can lead, initially, to a mis-diagnosis of cold haemmagglutinin disease (CHAD). Mixed-type AIHA is rare and can be idiopathic or secondary, often associated with systemic lupus erythematosus (SLE) and lymphoma. In general, patients with mixed-type AIHA show a dramatic response to steroid therapy and frequently require few or no transfusions. We report two unusual cases of mixed-type AIHA. Case one was unusual as the patient developed AIHA while on steroid medication. Case two, we believe, is the first reported case of splenic T cell angioimmunoblastic non-Hodgkins lymphoma (NHL) associated with mixed-type AIHA. The patient failed to respond to steroids, intravenous immunoglobulin, chemotherapy and treatment with rituximab. The patient received 33 units of red cells over a 9-week period. She finally underwent splenectomy with resolution of haemolysis. DAT tested with monospecific reagents, and thorough serological investigations is required to reach the diagnosis of mixed-type AIHA. Awareness of this condition is important as management may be different from either treating warm AIHA or CHAD.
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PMID:Mixed-type autoimmune haemolytic anaemia: unusual cases and a case associated with splenic T-cell angioimmunoblastic non-Hodgkin's lymphoma. 1745 98

This report describes experiments designed to (1) establish the specificity of dopamine (DA) transporter (DAT)-mediated plasmalemmal DA transport, vesicular monoamine transporter-2 (VMAT-2)-mediated vesicular DA transport, and K+-stimulated DA release in samples prepared from frozen rat striata, and (2) characterize the time-course of the effects of freezing on these processes. The procedure described herein uses a simple method of freezing brain tissue (first cooling in ice-cold buffer and then freezing at -80 degrees C) that allows for the storage of rat striata followed by the assay of DA transport and K+-stimulated DA release using rotating disk electrode voltammetry. Plasmalemmal DA transport into samples prepared from frozen striata was blocked by the DAT inhibitor, cocaine, and vesicular DA transport was blocked by the VMAT-2 inhibitor, dihydrotetrabenazine. Additionally, K+-stimulated DA release was Ca+2-dependent. Freezing decreases DAT-mediated DA transport, VMAT-2-mediated DA transport, and K+-stimulated DA release. However activity is still measurable even after 3 weeks of storage. These results suggest that rat striata retain some DA transport and DA release activity even when stored frozen for a few weeks. Frozen storage of rat striata may thus be valuable for experiments requiring lengthy assays, the accumulation of material, or the transport of samples from one laboratory to another for analysis. These results may also be applicable to the study of frozen human brain tissue.
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PMID:Measurement of plasmalemmal dopamine transport, vesicular dopamine transport, and K(+)-stimulated dopamine release in frozen rat brain tissue. 1946 19

Although evidence shows that several dopamine neurotransmission pathway genes are associated with specific clinical pain syndromes, such as fibromyalgia, chronic headache, and postoperative pain, the exact role of dopamine in pain processing is not fully understood. The aim of this study was to explore the relationship between functional polymorphisms in dopaminergic candidate genes and sensitivity to pain in healthy subjects. Healthy subjects (n=192; 105 F, 87 M) were exposed to experimental tonic cold pain (1 degrees C) and phasic heat pain (47 degrees C) stimuli. DNA samples were obtained from both participants and their parents. The relationships between pain response (intensity in response to heat and cold; threshold and tolerance in response to cold only) and the functional Variable Number of Tandem Repeat (VNTR) polymorphisms of three dopamine-related genes were investigated using a Transmission Disequilibrium Test (TDT). Specifically, 30-bp repeat in the promoter region of the monoamine oxidase-A gene (MAO-A), 40-bp repeat in the 3'-untranslated region of the dopamine transporter gene (DAT-1), and 48-bp repeat in the exon 3 of the dopamine receptor 4 gene (DRD4) were examined. Significant associations between cold pain tolerance and DAT-1 (p=0.008) and MAO-A (p=0.024) polymorphisms were found. Specifically, tolerance was shorter for carriers of allele 10 and the rarer allele 11, as compared to homozygous for allele 9, and for carriers of allele 4 as compared to homozygous for allele 3, respectively. These results, together with the known function of the investigated candidate gene polymorphisms, suggest that low dopaminergic activity can be associated with high pain sensitivity and vice versa.
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PMID:Associations between polymorphisms in dopamine neurotransmitter pathway genes and pain response in healthy humans. 1979 78

A case of hyperhemolytic transfusion reaction attributable to anti-Fy3 in a 30-year-oldAfricanAmerican woman with a history of sickle cell disease is reported. The patient was admitted for vaso-occlusive sickle cell crisis and received 4 units of packed RBCs secondary to worsening symptomatic anemia (Hb 5.0 g/dL). On admission, the patient's antibody screen and identification showed anti-V and anti-E, and her antibody history included anti-E,-C,-Jk(b),-N, -V,-S,-Sl(a), and a cold agglutinin with possible anti-I specificity. A DAT performed on her RBCs was negative. RBC units that lacked E, C, Jk(b), N,V, and S were transfused. Posttransfusion Hb was 8.9 g/dL. On day 10 she developed a fever of 103 degrees F, and on day 11 her Hb decreased to 6.4 g/dL. She complained of severe back pain and dark urine. In addition, she became hypertensive, tachycardic, and jaundiced. The DAT indicated the presence of IgG on the patient's RBCs. Anti-Fy3 was identified in the serum and eluate. During the next 24 hours, her Hb decreased to 2.4 g/dL. The LDH level was 1687 U/L, and her reticulocyte count was 2.6%. A delayed hemolytic transfusion reaction with hyperhemolysis secondary to anti-Fy3 was suspected and was successfully treated with IVIG and high-dose prednisone. To the best of our knowledge, this is the first published case of hyperhemolysis in sickle cell disease attributable to anti-Fy3.
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PMID:Hyperhemolytic transfusion reaction attributable to anti-Fy3 in a patient with sickle cell disease. 1985 30


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