Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.     

Poly(D,L-lactide/epsilon-caprolactone)/hydroxyapatite composites as bone filler: an in vivo study in rats

In this study, a novel composite bone substitute was implanted in animal models (rats) and their in vivo characteristics were examined. A D,L-lactide and E-caprolactone copolymer (Mw: 80,000; Mn:40,000, and PI:2.00) was synthesized by ring-opening polymerization of the respective dimers using stannous octoate as the catalyst. The final ratio of D,L-lactide to epsilon-caprolactone obtained by 1NMR was 60/40. Hydroxyapatite (HA) powder was loaded in the copolymer. The HA/copolymer ratio was 60/40 (w/w). These composites were easily shaped by hand. Animal tests were performed on mature wistar rats (n=30). Defects were created on the proximal, the thickest part of the femur. The bone defects of the first group were filled with polymer/HA composite, the second group filled with only HA and the third group was left empty. Histologic examination of bone tissues showed new bone formation around the yellow-green polymer/HA composite material in the first group of animals whereas no evidence of new bone growth was observed in other groups.     

Role of granulocyte colony-stimulating factor in the treatment of mucormycosis

Several problems in the management of life-threatening mucormycosis remain unresolved, necessitating new methods of management. Four patients with histopathologically proven rhinocerebral mucormycosis were treated with high cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had multiple predisposing factors for mucormycosis, particularly leukemia and neutropenia. Two patients refractory to fluconazole therapy were treated with liposomal amphotericin B. The improvement in clinical manifestations was closely related to neutrophil recovery, and all patients were alive at the end of therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems to have played a role in their survival.     

Method of quantitative anatomical study of the dorsal neck muscles

Summary Biomechanical models of the cervical spine require knowledge of the position, size and orientation of the individual muscles that act on the cervical spine. We have developed a technique to stereometrically measure anatomical specimens. The apparatus is composed of three graduated metallic rods, which slide along a fixed support. This method is accurate to map the anatomy of individual muscles and provides quantitative data on their lines of action. Results are obtained from one specimen. The computer processing of the collected data allows formulation of a three-dimensional model of the neck muscles in man.

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Méthode d'étude anatomique quantitative des muscles de la nuqueEtude préliminaire

Résumé Pour élaborer un modèle biomécanique de la colonne cervicale, il faut connaître la position, la taille et l'orientation des différents muscles du cou. Nous avons mis au point une méthode de mesure stéréométrique sur des sujets anatomiques. L'appareil est composé de 3 axes métalliques gradués qui coulissent sur un support fixe. Cette technique permet une étude anatomique précise de chacun des muscles de la nuque, fournissant des données quantitatives sur les différents faisceaux ou lignes d'action. Les résultats sont obtenus sur un sujet. Leur traitement informatique permettra l'élaboration d'un modèle mathématique tridimensionnel des muscles du cou chez l'homme.

     

Is there any correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human nonsmall cell lung cancer?

A potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis and adverse survival, is the L-myc gene. The studies of lung cancer patients from different populations have yielded controversial results. We studied 64 nonsmall cell lung cancer (NSCLC) patients and 37 healthy controls of Turkish origin for L-myc gene polymorphism. Our aim was to test the hypothesis that there was association between L-myc S allele in NSCLC and predisposition to the disease and TNM stage indicating tumor size, node classification and metastasis. Polymerase chain reaction restriction fragment length polymorphism and agarose gel electrophoresis were used to determine the L-myc oncogene genotypes. We found no significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data concerning age, sex, size of tumors, histological type of tumors showed no significant association with L-myc genotype. However, a higher frequency of L-myc S allele in the squamous cell carcinoma compared to other histological groups was found, although this difference was not statistically significant. No association was found between the L-myc RFLP and increased risk of metastasis either to the lymph nodes or to other organs. Our results suggested that L-myc gene polymorphism was not a suitable prognostic marker of metastatic development in Turkish NSCLC patients.     

Enhancing effect of chitosan on peptide drug delivery across buccal mucosa

The buccal mucosa represents a potentially important topical route for delivery of peptide or protein drugs with some unique advantages such as the avoidance of hepatic first-pass metabolism and the acidity and protease activity encountered in the gastrointestinal tract. However, the bioavailabilities or relative potencies of intraorally administered peptides are usually quite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has been claimed to act both as a bioadhesive and permeabilizer, making it a candidate system for mucosal drug delivery. In this study, the enhancement effect of chitosan in gel form for oral mucosa was investigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across porcine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chitosan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug.     

阿尔茨海默氏病和帕金森氏病对老年人认知功能及日常生活能力的影响分析

目的探讨阿尔茨海默氏病(AD)和帕金森氏病(PD)对老年人认知功能及日常生活能力的影响。方法对2000～2003年就诊于我院的53例AD、68例PD和60例正常人应用简易智力量表(MMSE)和日常生活能力量表(ADL)进行分析。结果AD组与对照组相比MMSE总分及各因子分、ADL总分及各单项分均有显著性差异(P<0.01):PD组与对照组相比除MMSE的记忆力和语言因子分以及ADL第13项目(打电话)外,其余均有显著性差异(P<0.05):AD组与PD组相比除ADL第7项(穿衣)外均有显著性差异(P<0.05)。结论AD和PD对老年人的认知功能和日常生活能力均有显著的影响,两者相比,AD对老年人的影响更严重、更广泛。     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.     

Creatine kinase activity associated with the contractile proteins of the guinea-pig carotid artery

Summary Activity and role of creatine kinase associated with contractile proteins of vascular smooth muscle have been investigated using skinned guinea-pig carotid artery rings. Membrane solubilization was performed with the detergent Triton X-100. Creatine kinase activity, isoenzyme profile as well as mechanics were performed on the Triton skinned carotid artery rings. Total creatine kinase activity was 47.3±9.3 IU g¹ ww and electrophoresis showed BB, MB, and MM isoforms (BB-CK being the predominant isoenzyme). One hour incubation with Triton X-100, produced predominantly BB-CK remaining with the myofibrils with some MB, representing 23% of the preskinned creatine activity. When relaxed carotid artery rings were exposed to pCa 9 in the presence of 250 M ADP, 0 ATP, and 12 mM phosphocreatine, tension was not significantly different from resting tension, but changing to pCa 4.5 caused the carotid artery rings to generate 49.5±4.5% of maximal tension. When a high-tension rigor state was achieved (250 M ADP, 0 ATP, 0 phosphocreatine, and pCa 9), the addition of 12 mM phosphocreatine effected significant relaxation. These observations implicate an endogenous form of creatine kinase, associated with the myofilaments, which is capable of producing enough ATP for submaximal tension generation and significant relaxation from rigor conditions. These results suggest co-localization of ATPase, MLCK, and creatine kinase on the contractile proteins of the carotid artery. Such an enzymic association may play a role in the energetic supply to the contractile apparatus of vascular smooth muscle.Recipient of INSERM/NIH Fogarty International Fellowship, TW01585-01.