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201.
FS Chen PE Di Cesare AA Kale JF Lee VH Frankel SA Stuchin JD Zuckerman 《Canadian Metallurgical Quarterly》1998,13(8):867-873
We have developed a computer program for the rapid assessment of the primary structure differences between a protein of unknown sequence and a homologous known protein. Both proteins are reduced, alkylated, and digested with the same hydrolytic agent. The unfractionated peptide mixtures are submitted to automatic sequence analysis. Based on the knowledge of the reference sequence, the program utilizes the analysis data to identify all the potential peptides present in the two mixtures, determining their primary structure, homology degree, and molecular weight calculated both as integer MH+ and average mass variables. These fingerprints allow the user to easily identify the structural differences between the two proteins and clarify possible doubts by a mass spectrometric analysis of the two mixtures. In order to verify the utility of the program, we provide an application example using the already reported data of two homologous proteins. 相似文献
202.
J Geisler SB Geisler PE L?nning R Smaaland KM Tveit H Refsum PM Ueland 《Canadian Metallurgical Quarterly》1998,4(9):2125-2128
We measured plasma total homocysteine (tHcy) in 14 patients (13 patients with colorectal cancer and 1 patient with breast cancer) during their first treatment with 5-fluorouracil (5-FU) plus leucovorin [LV (5-FULV)]. Eight of these patients were investigated a second time after 3-10 cycles (median, 4 cycles) with 5-FULV. Each cycle consisted of two administrations of 5-FU (500 mg/m2) and LV (60 mg/m2) given 24 h apart. The first administration of 5-FULV on day 1 of the first cycle induced a rapid reduction of the tHcy level from 12.5 micromol/liter (10.4-15.1 micromol/liter; geometric mean with 95% confidence interval of the mean) to 9.1 micromol/liter (7.5-11.1 micromol/liter) in 24 h. tHcy remained stable at this level after the second administration of 5-FULV. In addition, the 5-FULV regimen caused a concurrent 4-fold increase in both serum and erythrocyte folate. The fifth cycle with 5-FULV had only marginal effects on the tHcy level. 5-FU without LV modulation had no effect on the plasma tHcy or folate status in eight breast cancer patients. Our data establish the reduction of tHcy as a responsive indicator of LV pharmacodynamics. 相似文献
203.
MA Willemsen PE Jira FJ Gabre?ls AT van der Ploeg JA Smeitink 《Canadian Metallurgical Quarterly》1998,142(24):1388-1392
Three neonatal patients, one girl and two boys, presented with infantile Pompe's disease. A generalized hypotonia with decreased tendon reflexes and heart failure due to hypertrophic cardiomyopathy dominated the clinical picture in all three; these symptoms are uniformly and characteristically present. This autosomal recessive glycogen storage disease is caused by a deficiency of lysosomal alpha-glucosidase. The diagnosis, suspected on the basis of the characteristic clinical picture and the results of simple laboratory tests, is made by measurement of the enzymatic activity or DNA analysis. Most patients die in their first year of life, no treatment being available. 相似文献
204.
C Clark D Bast AM Sharp PM St Hilaire R Agha PE Stein EJ Toone RJ Read JL Brunton 《Canadian Metallurgical Quarterly》1996,19(4):891-899
The homopentameric B subunit of verotoxin 1 (VT1) binds to the glycosphingolipid receptor globotriaosylceramide (Gb3). We produced mutants with alanine substitutions for residues found near the cleft between adjacent subunits. Substitution of alanine for phenylalanine 30 (Phe-30) resulted in a fourfold reduction in B subunit binding affinity for Gb3 and a 10-fold reduction in receptor density in a solid-phase binding assay. The interaction of wild-type and mutant B subunits with Pk trisaccharide in solution was examined by titration microcalorimetry. The carbohydrate binding of the mutant was markedly impaired compared with that of the wild type and was too weak to allow calculation of a binding constant. These results demonstrate that the mutation significantly impaired the carbohydrate-binding function of the B subunit. To ensure that the mutation had not caused a significant change in structure, the mutant B subunit was crystallized and its structure was determined by X-ray diffraction. Difference Fourier analysis showed that its structure was identical to that of the wild type, except for the substitution of alanine for Phe-30. The mutation was also produced in the VT1 operon, and mutant holotoxin was purified to homogeneity. The cytotoxicity of the mutant holotoxin was reduced by a factor of 10(5) compared to that of the wild type in the Vero cell cytotoxicity assay. The results suggest that the aromatic ring of Phe-30 plays a major role in binding of the B subunit to the Galalpha1-4Galbeta1-4Glc trisaccharide portion of Gb3. Examination of the VT1 B crystal structure suggests two potential carbohydrate-binding sites which lie on either side of Phe-30. 相似文献
205.
AK Lalwani RK Jackler RW Sweetow ED Lynch H Raventós J Morrow MC King PE León 《Canadian Metallurgical Quarterly》1998,124(6):699-702
BACKGROUND: Autosomal dominant, nonsyndromic, hereditary hearing impairment in a large Costa Rican kindred is caused by a mutation in the human homolog of the Drosophila diaphanous gene. OBJECTIVE: To further characterize the phenotype of DFNA1 with comprehensive audiovestibular evaluation and computed tomography of the temporal bone. PATIENTS: One affected child and 2 affected adults of the Costa Rican kindred who harbor a mutation in the diaphanous gene. SETTING: Medical Center at the University of California, San Francisco. INTERVENTION: Otologic and neuro-otologic examination; pure tone audiometry, speech audiometry, and immitance testing; auditory evoked potentials, electrocochleography, and otoacoustic emissions; electronystagmography and vestibular autorotation tests; and computed tomography of the temporal bone. RESULTS: The youngest subject, an 8-year-old boy, had a mild hearing loss, intact stapedial reflexes, otoacoustic emissions at high frequencies, normal auditory evoked potentials, and electrocochleographic findings consistent with endolymphatic hydrops. The two adults had severe to profound bilateral sensorineural hearing impairment. Electronystagmography disclosed normal vestibular function. Computed tomography demonstrated normal external, middle, and inner ear structures. CONCLUSIONS: These results suggest that the early low-frequency hearing loss in this family is associated with endolymphatic hydrops. Elucidation of the role of the diaphanous gene in hearing will therefore lead to a better understanding of the mechanism of endolymphatic hydrops. 相似文献
206.
PB Vrtunski PE Konicki KY Kwon G Jurjus GE Jaskiw GJ Jaskiw 《Canadian Metallurgical Quarterly》1996,20(1-2):187-198
It is well established that clozapine is less likely than typical antipsychotic drugs to cause clinically discernible extrapyramidal side-effects. There is a paucity of data, however, on clozapine's motor effects. In this report we compare normal controls to groups of chronic schizophrenic patients treated with either typical antipsychotic drugs or with clozapine. Motor function was measured with a target-matching task, a test relying on submaximal sustained force control. Results indicated that patients on clozapine performed with significantly lower accuracy (greater variability) of force control. Even though the clozapine patients were treatment resistant to typical antipsychotic drugs, and many had a history of tardive dyskinesia, we postulate that the observed deficit is likely due to clozapine treatment rather than to earlier treatments or other factors. The observed force control deficit may be the result of an increase in myoclonus and a generally lower level of overall motor activity. 相似文献
207.
A 36-year-old male with unspecific symptoms and normal physical examination had right cardiac enlargement on chest X-ray. Two-dimensional echocardiographic and thoracic computed tomography demonstrated an intracardiac mass. The tumor was surgically resected and the pathological diagnosis was mixed-type epicardial hemangioma. We discuss this case and review the literature. 相似文献
208.
PL Appleton NC Ellis PE Minchom V Lawson V B?ll P Jones 《Canadian Metallurgical Quarterly》1997,22(5):707-722
Examined self-reported depressive symptoms in 72 young people with spina bifida, ages 9 to 18:11, and matched able-bodied comparison subjects, using the Dimensions of Depression Profile for Children and Adolescents (Harter & Nowakowski, 1987). Independent variables included gender, self-perceptions (including physical appearance), and perceived social support. Young people with spina bifida were at greater risk of depressive mood, low self-worth, and suicidal ideation. Girls, independent of disability, were at greater risk of depressive mood, low self-worth, and self-blame. Multiple regression analyses suggest that global self-worth serves as a mediating variable for the effect of physical appearance self-concept on depressed mood (particularly in young people with spina bifida), and that perceived parental social support has a direct effect on depressed mood (particularly in girls). 相似文献
209.
210.
The overlying retinal blood vessels were abnormal in five cases of congenital hypertrophy of the retinal pigment epithelium. This illustrated the well-recognized association between outer retinal degeneration and obliteration of the overlying retinal vasculature. The proposed pathophysiological mechanisms, however, seem inadequate to explain completely the morphological changes of the retinal blood vessels in the presence of atrophy of the outer retina. 相似文献