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71.
Monica Conciatori Christopher J Stodgell Susan L Hyman Melanie O'Bara Roberto Militerni Carmela Bravaccio Simona Trillo Francesco Montecchi Cindy Schneider Raun Melmed Maurizio Elia Lori Crawford Sarah J Spence Lucianna Muscarella Vito Guarnieri Leonardo D'Agruma Alessandro Quattrone Leopoldo Zelante Daniel Rabinowitz Tiziana Pascucci Stefano Puglisi-Allegra Karl-Ludvig Reichelt Patricia M Rodier Antonio M Persico 《Neuropsychopharmacology》2004,55(4):413-419
BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference. 相似文献
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Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation. 相似文献
75.
Abstract: The use of neuromuscular electrical stimulation (NMES) for rehabilitation of gait in spinal patients is widely known. The best results can be obtained with the use of biomechanical sensors and a closed loop NMES system. One of the biggest problems faced in the design of control systems for closed-loop operation, in gait rehabilitation, is the variation of the mechanical conditions during the phases of gait. This work presents a new approach to ease the design of rule-based closed loop systems for operation in conditions such as gait rehabilitation. 相似文献
76.
Megakaryocytic Progenitors Can Be Generated Ex Vivo and Safely Administered to Autologous Peripheral Blood Progenitor Cell Transplant Recipients 总被引:9,自引:1,他引:8
77.
Basilio Pispisa Mariano Venanzi Antonio Palleschi Maria D'Alagni 《Macromolecular chemistry and physics.》1995,196(9):2809-2825
The photophysics of protoporphyrin-naphthyl (P-N) pairs covalently and randomly bound to the ε-amino groups of the side-chains of poly(L -lysine) (PL) were investigated by steady-state and time-resolved fluorescence measurements. The results indicate that quenching of excited naphthalene (λex = 280 nm) chiefly occurs by interconversion to the triplet state when the polymeric matrix is in random coil (pH ≈ 7) and by intramolecular electron transfer from ground-state porphyrin, P → 1N*, when the polypeptide is in α-helical conformation (pH ≈ 11), the specific rate constant of the electron transfer being 3,1 · 107 s?1 (25°C). PNPL exhibits very little exciplex fluorescence, whatever the pH, suggesting both a reduced internal Brownian motion of the chromophores, owing to the amide bond in the substituted side-chains, and a relatively large average interprobe separation distance. This agrees with polarized fluorescence data and with the results of a conformational statistics analysis on the fully ordered PNPL, indicating that the average interchromophoric distance for which the electron transfer has the highest probability to occur is around 12 Å. The computational results allowed us to reproduce the experimental fluorescence decay curves and estimate the parameters governing the electron transfer process. Implications of these findings on the relaxation time of the heli-xcoil transition in PNPL are briefly discussed. 相似文献
78.
Jos Meseguer Antonio Lpez-Ruiz Alfonsa Garcí-Ayala 《Anatomical record (Hoboken, N.J. : 2007)》1995,241(3):303-309
Background: Head-kidney, considered the major fish lympho-haemopoietic tissue, consists of cells of the different haemopoietic series supported by a network of stromal cells whose morphofunctional properties have not been established. We report the ultrastructure and cytochemical features of the reticulo-endothelial stroma of the head-kidney from the seawater teleost gilthead seabream (Sparus aurata L.). Methods: Samples of head-kidney were processed for electron microscopic study. Some of the samples were incubated for acid and alkaline phosphatase, peroxidase, glucose-6-phosphatase, or ATPase. Results: The reticulo-endothelial stroma of gilthead seabream head-kidney consists of sinusoidal cells (endothelial and adventitial cells) and reticular cells (macrophage-type reticulum and fibroblast-like reticular cells). Transcytosis vesicles and rounded medium electron-dense granules were observed in the cytoplasm of the endothelial cells. The adventitial cells partially covered the outside surface of the endothelial cells and were joined by desmosomes. The macrophage-type reticulum cells were characterized by their cytoplasmic processes and acid phosphatase positive lysosomes. The fibroblast-like reticular cells were joined by desmosomes and formed an extensive network between the haemopoietic parenchyma. They were peroxidase negative and acid and alkaline phosphatase, glucose-6-phosphatase, β-glucuronidase, and ATPase positive. Conclusions: The ultrastructural and cytochemical features of the reticulo-endothelial stroma of the gilthead seabream head-kidney are similar to those of mammalian bone marrow, suggesting phylogenetic analogies between both tissues. © 1995 Wiley-Liss, Inc. 相似文献
79.
80.
Marco Vivarelli Alessandro Cucchetti Fabio Piscaglia Giuliano La Barba Luigi Bolondi Antonino Cavallari Antonio Daniele Pinna 《Liver transplantation》2005,11(5):497-503
To confirm recent observations about the relationship between immunosuppression and the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), we retrospectively analyzed 70 consecutive HCC patients who underwent LT and received cyclosporine (CsA)-based immunosuppression. CsA trough blood levels, measured with the same technique (fluorescence polarization immunoassay), were analyzed at different time points after transplantation. The exposure to the drug was calculated with the trapezoidal rule in each patient. CsA was associated with steroids in 26 patients and steroids and azathioprine in 44 patients. HCC recurred in 7 patients (10.0%). Different immunosuppressive schedules (CsA and steroids vs. CsA, steroids, and azathioprine) or the cumulative dosage of steroids and azathioprine did not influence HCC recurrence that was associated instead with CsA exposure (278.3 +/- 86.4 ng/mL in recurrent vs. 169.9 +/- 33.3 in tumor-free patients; P < 0.001); CsA exposure above 189.6 ng/mL was related to HCC recurrence at the receiver operating characteristic analysis (ROC). The relationship between CsA exposure; various clinical (sex, age, viral- vs. non-viral-related cirrhosis, preoperative vs. incidental diagnosis of HCC, alpha-fetoprotein [AFP] blood level), pathologic (pathologic tumor staging [pT] stage, presence of Milan criteria), and histologic (grading, presence of microvascular tumor invasion) parameters; and tumor recurrence were assessed. AFP (P = 0.032), microvascular tumor invasion (P = 0.044), and CsA exposure (P < 0.001) influenced recurrence-free survival at the univariate analysis; CsA exposure was the only independent prognostic determinant at multivariate analysis (P < 0.001). High CsA exposure favors tumor recurrence; CsA blood levels should be kept to the effective minimum in HCC patients. In the presence of pathologic and histologic risk factors, specific immunosuppressive protocols should be considered. 相似文献