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51.
KE Goodwill C Sabatier C Marks R Raag PF Fitzpatrick RC Stevens 《Canadian Metallurgical Quarterly》1997,4(7):578-585
Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure. 相似文献
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E Glaasker FS Tjan PF Ter Steeg WN Konings B Poolman 《Canadian Metallurgical Quarterly》1998,180(17):4718-4723
In this report, we compared the effects on the growth of Lactobacillus plantarum of raising the medium molarity by high concentrations of KCl or NaCl and iso-osmotic concentrations of nonionic compounds. Analysis of cellular extracts for organic constituents by nuclear magnetic resonance spectroscopy showed that salt-stressed cells do not contain detectable amounts of organic osmolytes, whereas sugar-stressed cells contain sugar (and some sugar-derived) compounds. The cytoplasmic concentrations of lactose and sucrose in growing cells are always similar to the concentrations in the medium. By using the activity of the glycine betaine transport system as a measure of hyperosmotic conditions, we show that, in contrast to KCl and NaCl, high concentrations of sugars (lactose or sucrose) impose only a transient osmotic stress because external and internal sugars equilibrate after some time. Analysis of lactose (and sucrose) uptake also indicates that the corresponding transport systems are neither significantly induced nor activated directly by hyperosmotic conditions. The systems operate by facilitated diffusion and have very high apparent affinity constants for transport (>50 mM for lactose), which explains why low sugar concentrations do not protect against hyperosmotic conditions. We conclude that the more severe growth inhibition by salt stress than by equiosmolal concentrations of sugars reflects the inability of the cells to accumulate K+ (or Na+) to levels high enough to restore turgor as well as deleterious effects of the electrolytes intracellularly. 相似文献
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C Teinturier MS Pauchard L Brugières P Landais JL Chaussain PF Bougnères 《Canadian Metallurgical Quarterly》1999,32(2):106-111
BACKGROUND: A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. PROCEDURES: Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. RESULTS: Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). CONCLUSIONS: In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials. 相似文献
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OBJECTIVE: Higher than normal cellular levels of the phospholipid catabolic intermediate glycerophosphocholine have been found in postmortem brain tissue of persons with Alzheimer's disease. Proton magnetic resonance spectroscopy (1H-MRS) can detect a choline resonance that is largely due to glycerophosphocholine. The authors tested the hypothesis that treatment with xanomeline, an M1 selective muscarinic cholinergic agonist, would be associated with a decrease in the 1H-MRS choline resonance. METHOD: Patients with mild to moderate Alzheimer's disease received placebo or xanomeline for 6 months. 1H-MRS spectra were collected at baseline and after treatment discontinuation for 12 patients, two taking placebo and 10 taking xanomeline at a dose of 25 mg t.i.d. (N = 4), 50 mg t.i.d. (N = 3), or 75 mg t.i.d. (N = 3). RESULTS: For the combined group of patients taking xanomeline, there was a significant decrease in the choline/creatine ratio from baseline to endpoint. CONCLUSIONS: Treatment of Alzheimer's disease with a cholinergic agonist is associated with a decrease in the MRS choline resonance. Xanomeline may reduce breakdown of cholinergic neuron membranes by reducing the cellular requirement for free choline for acetylcholine synthesis. 相似文献
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In order to evaluate hypotheses regarding production constraints on final consonants in babbling, 721 utterance-final consonants produced by 6 infants in consonant-vowel-consonant (CVC) syllables were examined and compared with the preceding consonant in the CVC. Consistent with earlier studies, major patterns were observed for each of the three main consonantal properties--place and manner of articulation and voicing. These patterns included a strong tendency for final consonants to repeat the place of articulation of nonfinal consonants and a tendency for relatively more fricative, nasal and voiceless consonants to occur in final position than in nonfinal position. The high frequency with which final consonants shared place of articulation with the preceding consonant was considered to reflect 'frame dominance' or the tendency of a relatively constant mandibular cycle (the frame) to determine the structure of utterances with very little contribution from other active articulators. The manner and voicing effects were attributed to an overall terminal energy decrease in the vocal production system. 相似文献
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The emission spectrum of TiCl has been investigated in the 3000-12 000 cm-1 region at high resolution using a Fourier transform spectrometer. The bands were excited in a microwave discharge through a flowing mixture of TiCl4 and helium. The observed bands have been classified into three electronic transitions, C4Delta-X4Phi, G4Phi-X4Phi, and G4Phi-C4Delta. In the 3000-3500 cm-1 region, four bands with R heads at 3368.7, 3331.8, 3291.9, and 3243.4 cm-1 have been assigned as the 0-0 bands of the 1/2-3/2, 3/2-5/2, 5/2-7/2, and 7/2-9/2 subbands, respectively, of the C4Delta-X4Phi transition. To higher wavenumbers, four transitions with 0-0 R heads at 10 930.7, 10 921.3, 10 906.5, and 10 886.9 cm-1 have been assigned as the 3/2-3/2, 5/2-5/2, 7/2-7/2, and 9/2-9/2 subbands, respectively, of the G4Phi-X4Phi system of TiCl. Four additional bands with 0-0 R heads at 7568.8, 7596.4, 7622.2, and 7651.7 cm-1 have been identified as the 1/2-3/2, 3/2-5/2, 5/2-7/2, and 7/2-9/2 subbands of the G4Phi-C4Delta transition, respectively. A rotational analysis of a number of vibrational bands of these transitions has been obtained and molecular constants have been extracted. The lowest 4Phi state has been assigned as the ground state of TiCl, by analogy with our recent work on TiF (R. S. Ram and P. F. Bernath, J. Mol. Spectrosc., in press). The correspondence between the electronic states of TiCl, TiF, TiH, and Ti+ is also discussed. Copyright 1997 Academic Press. Copyright 1997Academic Press 相似文献
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