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)

We present clinico-pathological correlations for a consecutive series of 44 demented patients in the Vienna longitudinal study on dementia. Prospective clinical diagnosis used the DSM-III-R and the NINCDS-ADRDA criteria. Not only the clinical, but also the neuropathological diagnosis of DAT is based on exclusion criteria, and depends on the interpretation of minimal vascular lesions. Although we did not exclude atypical cases from the study, 80% of diagnoses could be validated at autopsy. Nevertheless, our set of clinical criteria needs further validation in patients in the earliest stages of dementia.
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PMID:[Differential diagnosis of dementia diseases. A prospective clinical study with neuropathologic diagnostic verification]. 192 79

2,4-Diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are equally genotoxic in the Ames/Salmonella assay and are both readily absorbed, metabolized, and excreted and metabolites of both compounds are mutagenic with metabolic activation. However, there are marked differences in the results of chronic rodent bioassays with these two compounds. 2,4-DAT is a potent hepatocarcinogen whereas 2,6-DAT failed to produce an increased incidence of tumors in any tissue even when administered at a dose higher than that of 2,4-DAT. In an effort to elucidate the source of these apparently discordant results, the present studies were designed to determine the effects of these two chemicals on cell proliferation in the liver when administered at the dose levels comparable to those used in the original bioassays. This study utilized repeated oral dosing, osmotic minipumps to deliver bromodeoxyuridine (BrDU) for 8 days, and immunohistochemistry to quantitate BrDU incorporation into hepatic DNA, CCl4 (0.4 ml/rat, single ip dose) or vehicle control groups were included as positive and negative controls, respectively. The degree of cell proliferation was quantified by the labeling index from at least 1000 hepatocytes. Results from the control studies indicate that approximately 1.1% of the hepatocytes from vehicle-treated animals replicated during the exposure period whereas approximately 50% replicated in the positive controls. The carcinogen 2,4-DAT produced a dose-dependent increase in cell proliferation of approximately 10% and 20% in livers of animals exposed to 12.5 and 25.0 mg/kg/day, respectively, whereas the noncarcinogen 2,6-DAT produced no increase in cell turnover compared to vehicle control following treatment with 25.0 or 50.0 mg/kg/day. These results indicate a positive correlation between increased cell proliferation and hepatocarcinogenesis induced by these two isomers of diaminetoluene.
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PMID:Correlation of hepatocellular proliferation with hepatocarcinogenicity induced by the mutagenic noncarcinogen:carcinogen pair--2,6- and 2,4-diaminotoluene. 200 Jun 42

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.
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PMID:A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia. 201 79

In this study, vascular dementia (VD, 31 cases), senile dementia of Alzheimer type (DAT, 36 cases) and mixed type dementia (14 cases) were studied by means of magnetic resonance imaging (MRI). Diagnosis of dementia was made according to DSM-III and Hachinski's ischemic score. The areas of periventricular high intensity lesions (PVH) and those of brain parenchyma were measured by digitizer which was connected to a computer. The PVH score was obtained by dividing the areas of PVH by those of brain parenchyma at the level of the body of the lateral ventricule. A multiple variable analysis was applied to the PVH scores and risk factors for dementia using Hayashi's quantification method I. The multiple correlation coefficient between the PVH and the risk factors was 0.685. The most significant correlation was found between Hachinski's ischemic score and the PVH score (partial correlation coefficient: 0.58). Significant correlations were also found between ADL and the PVH score (0.25), as well as between the Hasegawa dementia score and the PVH score (0.24). Using the student T test, it was shown that the large PVH group was significantly correlated to poor ADL, whereas the small PVH group was not. The large PVH group in VD showed lower Hasegawa score than the small PVH group. On the other hand, there was no such correlation in DAT. PVH with prolongation of T2 could exist in various pathological states irrespective of their causes. Diffuse PVH tended to be frequently observed in VD together with poor ADL. It was therefore thought that brain ischemia was the main cause of PVH.
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PMID:[Clinical significance of periventricular high intensity lesions on magnetic resonance imaging in dementia]. 206 92

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
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PMID:High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. 206 54

Semiquantitative histological evaluation of brain iron and ferritin in Parkinson's (PD) and Alzheimer's disease (DAT) have been performed in paraffin sections of brain regions which included frontal cortex, hippocampus, basal ganglia and brain stem. The results indicate a significant selective increase of Fe3+ and ferritin in substantia nigra zona compacta but not in zona reticulata of Parkinsonian brains, confirming the biochemical estimation of iron. No such changes were observed in the same regions of DAT brains. The increase of iron is evident in astrocytes, macrophages, reactive microglia and non-pigmented neurons, and in damaged areas devoid of pigmented neurons. In substantia nigra of PD and PD/DAT, strong ferritin reactivity was also associated with proliferated microglia. A faint iron staining was seen occasionally in peripheral halo of Lewy bodies. By contrast, in DAT and PD/DAT, strong ferritin immunoreactivity was observed in and around senile plaques and neurofibrillary tangles. The interrelationship between selective increase of iron and ferritin in PD requires further investigation, because both changes could participate in the induction of oxidative stress and neuronal death, due to their ability to promote formation of oxygen radicals.
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PMID:Brain iron and ferritin in Parkinson's and Alzheimer's diseases. 207 10

To test whether changes in basic biochemical membrane constituents were reflected in membrane fluidity measurements, protein, total lipids, triglycerides, lecithin, cholesterol and alkaline phosphatase were determined in frontal cortex, hippocampus, putamen and nucleus basalis Meynert (NbM) of DAT brains and controls and compared to differential scanning thermograms. Biochemical changes were most pronounced in the hippocampus, while thermostability was altered in the NbM and the frontal cortex. The results indicate that changes in protein content, but not in lipid composition were reflected in alterations of thermostability of the brain regions examined.
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PMID:Reflection of changes in membrane constituents in various regions of Alzheimer brains to differential scanning thermograms. 208 96

Seventy-two consecutive and previously untreated adults with acute non-lymphoblastic leukaemia (ANLL), having a median age of 36 years (range 12 to 71), were prospectively randomised to receive conventional doses of cytosine arabinoside and doxorubicin combined with either etoposide (CTR III) or 6-thioguanine (DAT). Morbidity was comparable between the two regimens and complete remission (CR) rates of 52% and 62% respectively (p greater than 0.50) were not influenced by age above or below 50 years, initial white cell count, French-American-British classification, or race. However, growth pattern in the GM: CFUc assay was found to identify a subgroup of patients who had a significantly higher CR rate. Similarly, the secretion of tissue plasminogen activator by leukaemic blasts in vitro uniformly predicted for primary drug resistance, whereas a CR rate of 68% was associated with production of the urokinase type or a mixture of both enzymes. Remission duration and survival did not differ between these two forms of chemotherapy, nor were they influenced by immunotherapy with C. parvum or the duration of maintenance therapy, whereas age below 50 and the species of plasminogen activator secreted were significant prognostic factors. It is concluded that etoposide can be substituted for 6-thioguanine in these cytosine arabinoside and doxorubicin-containing regimens and that for both combinations the most sensitive prognostic factor for CR and survival is the species of plasminogen activator secreted in vitro by the leukaemic blasts.
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PMID:Chemotherapy of adult acute nonlymphoblastic leukaemia. 220 94

3-Iodo-6-methoxybenzamide (123I-IBZM), a new Dopamine D2 receptor ligand, was used in conjunction with SME 810 brain tomography to study six subjects (one normal volunteer, four schizophrenics and one DAT patient). Initial Dynamic SPET was followed by multislice SPET. High-resolution images of the D2 receptor distribution in the basal ganglia were obtained. The specific binding in D2 receptors of the basal ganglia is highest from 2-4 h p.i. Patients on anti-psychotic drugs showed significantly lower specific binding. Dopamine D2 brain receptor availability in man may now be studied with SPET. Continuous data acquisition with single slice tomography is particularly important in the study of this type of radiotracers.
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PMID:In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans. 220 50

The performance of 11 Alzheimer's (DAT) and 8 anomic aphasic stroke patients is contrasted with that of 32 normal elderly subjects on both the Boston Naming Test (BNT) and the Controlled Oral Word Association Test (COW), a letter-category verbal-fluency test. While both tests require phonological processing, only the BNT requires semantic processing (object recognition). Both DAT and anomic aphasic stroke patients were significantly impaired on the BNT, with mean z scores (based on the performance of the normals) of -4.08 and -2.57, respectively; the DAT patients were significantly farther from normal than were the anomic aphasics. Their relative levels of impairment on the COW were reversed: The anomic aphasics' performance (z = 1.79) was worse than that of the DATs (z = -0.66). This pattern of performance on the two tests is consistent with the hypothesis that impaired word finding reflects impaired processing mainly of semantic information for the DAT subjects, mainly of lexical-phonological information for the anomic aphasic subjects.
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PMID:Dysnomia in dementia and in stroke patients: different underlying cognitive deficits. 221 80


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