Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

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.     

A Paradigm for Design of Closed Loop Neuromuscular Electrical Stimulator Control Systems

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.     

Photoinduced electron transfer in porphyrin-naphthyl pairs covalently and randomly bound to α-helical poly(L-lysine)

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 (λ_ex = 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.     

Reticulo-endothelial stroma of the head-kidney from the seawater teleost gilthead seabream (Sparus aurata L.): An ultrastructural and cytochemical study

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.     

Biochemical and biological activity of the anthracycline analog, 4-demethyl-6-0-methyl-doxorubicin

Summary The chromophore-modified derivative of doxorubicin, 4-demethyl-6-0-methyl-doxorubicin, has been tested for antitumor activity in a range of experimental murine tumor systems. In contrast to the inactive 6-0-methyl derivative of daunorubicin, 4-demethyl-6-0-methyl-doxorubicin provided antitumor effects comparable to that of the parent compound. In addition, detailed DNA-interaction studies showed that the doxorubicin derivative retains the ability to bind DNA by the intercalation mechanism. However, the binding affinity was appreciably reduced following structural modification in the anthraquinone chromophore. On the basis of the proposed models of intercalation, these results could be rationalized in terms of steric influence of the bulky methoxy group. The results of this study are in agreement with the correlation already observed between DNA binding and relative antitumor activity of anthracyclines.     

Successful Liver and Kidney Transplantation From Cadaveric Donors With Left-Sided Bacterial Endocarditis

Bacterial infections are frequent in cadaveric organ donors and can be transmitted to the transplantation recipient, which could have devastating consequences for the recipients if adequate preventive measures are not adopted.
From the 355 consecutive brain dead cadaveric organ donors procured at our center in the last four years, 2000–2003, four of them (1.1%) had bacterial endocarditis as cause of death. The bacteria responsible for the endocarditis were Staphylococcus epidermidis, coagulase-negative Staphylococcus , Staphylococcus hominis and Streptococcus viridans , respectively. We performed five kidney and two liver transplantations on seven recipients. All donors and recipients received antibiotic treatment against the germ causing the respective endocarditis.
Infection by the bacteria responsible for the endocarditis in the respective donors was not transmitted to any of the recipients. Six of the seven recipients were alive with normal-functioning grafts after between 13 and 24 months' follow-up. Transplantectomy was performed on one kidney recipient due to thrombosis of the renal vein of the graft not related to the endocarditis.
Liver and kidney transplantation from donors dying from bacterial endocarditis can be performed without causing the transmission of infection to the recipient or the dysfunction of the graft.