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101.
Magnetic resonance imaging in juvenile Canavan disease 总被引:2,自引:0,他引:2
P. B. Toft R. Geiß-Holtorff M. O. Rolland O. Pryds W. Müller-Forell E. Christensen W. Lehnert H. C. Lou D. Ott J. Hennig O. Henriksen 《European journal of pediatrics》1993,152(9):750-753
We present a 2-year-old boy and a 6-year-old girl with mild Canavan disease (CD). Aspartoacylase activity in skin fibroblasts was deficient. Magnetic resonance imaging (MRI) of the brain did not show the prominent leucodystrophy previously reported in CD, but there was a hyperintense signal from the lentiform nuclei and the heads of the caudate nuclei on the T2-weighted MR images. This suggests a specific vulnerability of the corpus striatum in these patients. In the older patient, the white matter became affected at the age of 6 years. Proton magnetic resonance spectroscopy (1H-MRS) of white matter revealed a normal concentration of N-acetyl-l-aspartate (NAA) and a markedly decreased concentration of choline containing compounds (Cho) in the boy but a normal ratio of NAA to Cho in the girl. We conclude that deficient NAA catabolism affects myelin metabolism. This may present as changes in the striatum and/or as a low concentration of Cho before leucodystrophy appears on MRI. 相似文献
102.
103.
Anwer K Logan M Tagliaferri F Wadhwa M Monera O Tung CH Chen W Leonard P French M Proctor B Wilson E Singhal A Rolland A 《Pharmaceutical research》2000,17(4):451-459
Purpose. To design, synthesize, and test synthetic glycopeptide-baseddelivery systems for gene targeting to hepatocytes by systemicadministration.Methods. All peptides were synthesized by the solid phase methoddeveloped using Fmoc chemistry on a peptide synthesizer. The bindingof galactosylated peptides to HepG2 cells and accessibility of thegalactose residues on particle surface was demonstrated by acompetition assay using 125I-labeleld asialoorosomucoid and RCA lectinagglutination assay, respectively. DNA plasmid encoding chloramphenicolacetyl transferase (CAT) gene was complexed with a tri-galactosylatedpeptide (GM245.3) or tri-galactosylated lipopeptide (GM246.3) in thepresence of an endosomolytic peptide (GM225.1) or endosomolyticlipopeptide (GM227.3) to obtain DNA particles of 100–150 nm insize. The plasmid/peptide complexes were added to HepG2 cell culturesor intravenously administered by tail vein injection into normal miceor rats. Plasmid uptake and expression was quantified by qPCR andELISA, respectively.Results. Multiple antennary glycopeptides that have the ability tocondense and deliver DNA plasmid to hepatocytes were synthesized andcomplexed with DNA plasmid to obtain colloidally stable DNA/peptidecomplexes. Addition of DNA/GM245.3/GM225.1 peptide complexes(1:3:1 (–/+/–)) to HepG2 cell cultures yielded CAT expression intransfected cells. The transfection efficiency was significantly reducedin the absence of galactose ligand or removal of endosomolytic peptide.Intravenous administration of DNA/GM245.3 peptide complexes (1:0.5(–/+)) into the tail vein of normal rats yielded DNA uptake in theliver. Substitution of GM245.3 by galactosylated lipopeptide GM246.3resulted in more stable DNA particles, and a 10-fold enhancement inliver plasmid uptake. CAT expression was detectable in liver followingintravenous administration of DNA/GM246.3 complexes. Addition ofendosomolytic lipopeptide GM227.3 into the complexes(DNA/GM246.3/GM227.3 (1:0.5:1 (–/+/–))) yielded a 5-fold increase inCAT expression. Liver expression was 8-fold and 40-fold higher thanlung and spleen, respectively, and localized in the hepatocytes only.The transfection efficiency in liver was enhanced by increasing DNAdose and injection volume. The plasmid uptake and expression in liverusing DNA/GM246.3/GM227.3 complexes was 100-200-fold higherthan DNA formulated in glucose. Tissue examination and serumbiochemistry did not show any adverse effect of the DNA/GM246.3/GM227.3 (1:0.5:1 (–/+/–)) complexes after intravenous delivery.Conclusions. Gene targeting to hepatocytes was achieved by systemicadministration of a well-tolerated synthetic glycopeptide-baseddelivery system. The transfection efficiency of this glycopeptide deliverysystem was dependent on peptide structure, endosomolytic activity,colloidal particle stability, and injection volume. 相似文献
104.
105.
Cochat P Koch Nogueira PC Mahmoud MA Jamieson NV Scheinman JI Rolland MO 《The Journal of pediatrics》1999,135(6):746-750
OBJECTIVES: Survey on the current medical approach to and the economic issues affecting infants with primary hyperoxaluria type 1. METHODS: Questionnaire to specialized centers worldwide. RESULTS: Seventy-eight infants were identified: 44% were of Muslim origin and 56% were not. The consanguinity rate was 76% and 0%, respectively. Thirty-three percent were treated in developing countries (group 1) and 67% in developed countries (group 2). Initial presentation (4.9 +/- 2.8 months) consisted of failure to thrive (22%), urinary tract infection (21%), and uremia (14%). Radiologic findings included nephrocalcinosis (91%), urolithiasis (44%), or both (22%). The diagnosis was based on family history, tissue biopsy, and urine oxalate level in most patients from group 1 and on urine oxalate and glycolate levels, alanine:glyoxalate aminotransferase activity, and DNA analysis in patients from group 2. Therapeutic withdrawal was the final option for 40% of children; financial reasons were given for 10 of 17 patients from group 1 and 0 of 9 from group 2. End-stage renal disease started at 3.2 +/- 6.4 years of age and was present in half of the patients at the time of diagnosis. Fifty-two percent of the patients died: 82% in group 1 versus 33% in group 2; 33% of patients who underwent transplantation died versus 71% of those who did not. CONCLUSION: The management of primary hyperoxaluria type 1 in infants is a major example of the ethical, epidemiologic, technical, and financial challenges that are raised by recessive inherited diseases with early life-threatening onset. In certain circumstances, oxalosis can be regarded as a condition for which therapeutic withdrawal may be an acceptable option. 相似文献
106.
P F van der Heijden R E Lapp?hn R S Corbey W B de Goeij J Brownell R Rolland 《Fertility and sterility》1989,52(4):574-579
Forty-one hyperprolactinemic women (prolactin [PRL] greater than 2,000 mU/L) were treated between 12 and 52 weeks with the new nonergot, long-acting dopamine agonist octahydrobenzo [g] quinoline (CV 205-502). The treatment resulted in normalization of PRL secretion in 71% of the women at a once-daily dose of less than or equal to 0.100 mg. All women responded with a significant decrease in serum PRL. Menstrual function normalized in all women except 1, whereas galactorrhea disappeared in all but 2 patients. During the observation period, four pregnancies were recorded with an additional three in the immediate posttreatment period. Until now, four healthy children have been born. Regarding tolerability, women with fair or poor response bromocriptine (Parlodel) in the past tolerated CV 205-502 better. Two women with no PRL decrease while on Parlodel responded with a decrease while on CV 205-502. All safety parameters remained normal while on treatment, and no significant changes were observed in blood pressure (supine and standing), pulse rate, or electrocardiogram (ECG) recordings. CV 205-502 therefore seems to be a valuable new compound in the management of patients with hyperprolactinemia. 相似文献
107.
L.J. Van Dam R. Rolland 《European journal of obstetrics, gynecology, and reproductive biology》1981,12(5):323-330
The prolactin-lowering and lactation-inhibiting effects of lisuride and bromocriptine, two dopaminergic drugs, were compared in a double-blind study. Twenty-six women took lisuride, 0.2 mg b.i.d., and 24 women took bromocriptine, 2.5 mg b.i.d., during 14 days postpartum. Though both drugs gave satisfactory inhibition of puerperal milk production, in these dosages bromocriptine was a more effective lactation inhibitor and prolactin suppressor. After discontinuation of treatment rebound symptoms were more pronounced in the bromocriptine group than in the lisuride group. 相似文献
108.
P. M. Martin P. H. Rolland J. Jacquemier A. M. Rolland M. Toga 《Cancer chemotherapy and pharmacology》1979,2(2):115-120
Summary Histopathologic features (tumor cell density, histological type, and histoprognostic grade) were analyzed in 314 breast cancers investigated for estrogen (E) and progestin (P) receptors (R). The presence of PR is associated with the presence of ER. A relationship was found between the acinoductal differentiation of the lesions and the presence of SR: the more differentiated the carcinoma, the higher the frequency of ER. HPG III carcinomas have the lowest frequency of positive ER and HPG I tumors the opposite: the likelihood of the presence of SRs is inversely correlated with HPG. No statistically significant relationship existed between tumor cell density (TCD) and the presence of ER or ER content. Similar findings were observed for the stromal reaction. The results are discussed with respect to the biological significance of SR and histopathologic features: SR presence could be correlated with (1) a differentiated state of the tumors and (2) a slow rate of cellular replication. 相似文献
109.
110.