A novel helix termination mutation in keratin 10 in annular epidermolytic ichthyosis, a variant of bullous congenital ichthyosiform erythroderma

Annular epidermolytic ichthyosis is a distinct phenotypic variant of bullous congenital ichthyosiform erythroderma that has recently been described in two separate kindreds. Individuals with this variant present with bullous ichthyosis in early childhood and hyperkeratotic lichenified plaques in the flexural areas and extensor surfaces at later ages. Characteristically, they also develop intermittent bouts of annular and polycyclic, erythematous, scaly plaques on the trunk and proximal extremities. We now describe a third kindred with annular epidermolytic ichthyosis. Molecular analysis of this family revealed a novel mutation resulting in an isoleucine to threonine substitution at residue 107 (codon 446) within the highly conserved helix termination motif at the end of the rod domain of keratin 10.     

PURIFICATION OF THE CELLULAR RECEPTOR OF AN OYSTER JUICE BORNE COLIPHAGE OJ367 FROM THE OUTER MEMBRANE OF ESCHERICHIA COLI HOST

The cellular receptor of an oyster juice borne phage OJ367 was found in the outer membrane (OM) of its host Escherichia coli. The total cell envelope (TCE) was fractionated by differential extraction and it was found that the OM possesses phage neutralization ability. The OM was purified by diethylaminoethyl cellulose column chromatography to screen for the phage recognition moiety. A homogeneous, 39‐kDa OM protein (Omp) with receptor activity was eluted. It was a peptidoglycan (PG)‐associated protein which showed trypsin resistance. Lipopolysaccharide (LPS) had no effect on its receptor activity either when coexisting in the column fractions or when the isolated LPS was mixed with the Omp. Mutants resistant to lysis by phage OJ367 were isolated. The amount of the 39‐kDa and another PG‐associated 37‐kDa protein decreased significantly in the TCE of the mutant. The 39‐kDa Omp may serve as the cellular receptor for adherence of the coliphage, whereas the 37‐kDa protein is also involved in the infection mechanism.     

A prospective study of short- and long-term neuropsychological outcomes after traumatic brain injury in children.

Longitudinal neuropsychological outcomes of traumatic brain injury (TBI) were investigated in 53 children with severe TBI, 56 children with moderate TBI, and 80 children with orthopedic injuries only. Neuropsychological functioning was assessed at baseline, at 6- and 12-month follow-ups, and at an extended follow-up (a mean of 4 years postinjury). Mixed model analyses revealed persistent neuropsychological sequelae of TBI that generally did not vary as a function of time postinjury. Some recovery occurred during the first year postinjury, but recovery reached a plateau after that time, and deficits were still apparent at the extended follow-up. Further recovery was uncommon after the first year postinjury. Family factors did not moderate neuropsychological outcomes, despite their demonstrated influence on behavior and academic achievement after childhood TBI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Osteocalcin and osteonectin immunoreactivity in the diagnosis of osteosarcoma

Osteosarcomas (OSAs) can be difficult to distinguish histologically from tumors with significantly different biologic potentials and treatment protocols. The correct diagnosis of OSA relies on identification of malignant osteoblasts that are capable of producing neoplastic bone. To determine the use of immunohistochemistry for the diagnosis of OSA, 106 tumors from the Massachusetts General Hospital and the University of Vermont were immunostained with monoclonal antiosteocalcin (OC) and antiosteonectin (ON) antibodies. They included 42 OSAs, 25 non-bone-forming sarcomas, 24 other malignant tumors including lymphomas, carcinomas, and melanomas, and 15 benign bone tumors. Cytoplasmic staining with OC showed 70% sensitivity and 100% specificity, while staining with ON showed 90% sensitivity and 54% specificity for bone-forming tumors, consistently staining cell types other than osteoblasts. Of the OSAs, 83% demonstrated matrix staining with one or both antibodies, whereas dense collagen was negative for both antibodies in all tumors. We conclude that tumor cell cytoplasmic staining with monoclonal OC may be helpful in distinguishing OSAs from other malignancies, and staining of extracellular matrix for OC and ON antibodies concurrently may help distinguish bone matrix from dense collagen.     

Lipoblastoma. A rare, benign tumor in children

Lipoblastoma is a rare, benign tumour of embryonal fat seen almost exclusively in infancy and early childhood. It occurs mostly in the extremities, but it is also seen in other parts of the body. The tumour may grow rapidly, and the fact that lipoblastomas show immature fat cells could lead to the wrong diagnosis of liposarcoma. Complete surgical excision appears to be the treatment of choice. A correct, preoperative diagnosis is possible in most cases. Two cases of lipoblastoma of the upper limb and one case in the scapular region are reported.     

BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal

Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, sun sensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS, and BLM protein is homologous to DNA helicase. There are two putative nuclear localization signals (NLSs) within amino acid residues 1334-1349 in the C-terminus of the BLM protein, which has the distinctive structure of two basic residue arms separated by a spacer. The entire coding or deleted BLM sequences of various sizes were ligated into an enhanced green fluorescent protein (EGFP) vector and transfected into HeLa cells. The EGFP vector harboring the entire BLM coding sequence was transported to the nucleus. The BLM protein truncated at 1341 amino acid, containing an intact helicase domain and only one proximal arm, was not transported to the nucleus. The BLM protein truncated at 1357 amino acid, containing an intact helicase domain and two arms, was transported to the nucleus. The EGFP vector harboring DNA fragments encoding a protein having only the distal arms of basic amino acids in the C-terminus was also transported to the nucleus. The truncated BLM proteins corresponding to previously reported mutated BLM proteins were retained in the cytoplasm or both the cytoplasm and the nucleus as was the EGFP vector with no insert. These results show that the BLM protein translocates into the nucleus and that the distal arm of the bipartite basic residues in the C-terminus of the BLM protein is essential for targeting the nucleus.     

基于频域系统辨识和支持向量机的桥梁状态监测方法

随着大跨度悬索、斜拉桥的增加,保障桥梁安全、降低维护费用成为交通管理以及政府部门关注的问题。针对损伤样本难以获得的实际情况,将桥梁状态监测问题作为模式识别中的“一类学习”问题处理。桥梁模式特征获取过程是“只有输出响应”的系统辨识问题,考虑到监测系统需要在线工作的特点,提出运用概念直观、结果可靠且便于自动实现的CMIF系统辨识方法作为获取模式特征的工具。为了获得足够敏感的异常报警判别函数,采用了基于支持向量机的一类学习算法,这种方法在得到很高灵敏性的同时,可以方便地权衡敏感性和泛化性能之间的矛盾。用香港汀九桥794小时实测数据对所采用的算法进行验证,证明了算法的有效性和实用性,其结果可供设计类似监测系统时参考。     

CD4-CD8-C.B-17 SCID thymocytes enter the CD4+CD8+ stage in the presence of neonatally grafted T cells

Our previous studies in iron-loaded rat heart cells showed that in vitro iron loading results in peroxidative injury, manifested in a marked decrease in rate and amplitude of heart cell contractility and rhythmicity, which is correctable by treatment with deferoxamine (DF). In the present studies we explored the role of mitochondrial damage in myocardial iron toxicity. Iron loading by 24-hour incubation with 0.36 mmol/L ferric ammonium citrate resulted in a decrease in the activity of nicotinamide adenine dinucleotide (NADH)-cytochrome c oxidoreductase (complex I+III) to 35.3%+/-11.2% of the value in untreated controls; of succinate-cytochrome c oxidoreductase (complex II+III) to 57.4%+/-3.1%; and of succinate dehydrogenase to 63.5%+/-12.6% (p < 0.001 in all cases). The decrease in activity of other mitochondrial enzymes, including NADH-ferricyanide reductase, succinate ubiquinone oxidoreductase (complex II), cytochrome c oxidase (complex IV), and ubiquinol cytochrome c oxidoreductase (complex III), was less impressive and ranged from 71.5%+/-15.8% to 91.5%+/-14.6% of controls. That the observed loss of respiratory enzyme activity was a specific effect of iron toxicity was clearly demonstrated by the complete restoration of enzyme activities by in vitro iron chelation therapy. Sequential treatment with iron and doxorubicin caused a loss of complex I+III and complex II+III activity that was greater than that seen with either agent alone but was only partially correctable by DF treatment. Alterations in cellular adenosine triphosphate measurements paralleled very closely the changes observed in respiratory complex activity. These findings demonstrate for the first time the impairment of cardiac mitochondrial respiratory enzyme activity caused by iron loading at conditions formerly shown to produce severe abnormalities in contractility and rhythmicity.     

TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption

A newly identified member of the tumor necrosis factor receptor (TNFR) superfamily shows activities associated with osteoclastogenesis inhibition and fibroblast proliferation. This new member, called TR1, was identified from a search of an expressed sequence tag database, and encodes 401 amino acids with a 21-residue signal sequence. Unlike other members of TNFR, TR1 does not contain a transmembrane domain and is secreted as a 62 kDa glycoprotein. TR1 gene maps to chromosome 8q23-24.1 and its mRNA is abundantly expressed on primary osteoblasts, osteogenic sarcoma cell lines, and primary fibroblasts. The receptors for TR1 were detected on a monocytic cell line (THP-1) and in human fibroblasts. Scatchard analyses indicated two classes of high and medium-high affinity receptors with a kD of approximately 45 and 320 pM, respectively. Recombinant TR1 induced proliferation of human foreskin fibroblasts and potentiated TNF-induced proliferation in these cells. In a coculture system of osteoblasts and bone marrow cells, recombinant TR1 completely inhibited the differentiation of osteoclast-like multinucleated cell formation in the presence of several bone-resorbing factors. TR1 also strongly inhibited bone-resorbing function on dentine slices by mature osteoclasts and decreased 45Ca release in fetal long-bone organ cultures. Anti-TR1 monoclonal antibody promoted the formation of osteoclasts in mouse marrow culture assays. These results indicate that TR1 has broad biological activities in fibroblast growth and in osteoclast differentiation and its functions.     

Outcome of obstructive uropathy after pelvic irradiation in patients with carcinoma of the uterine cervix

A prospective, randomized study was performed to assess the effectiveness of postoperative closed suction drainage. One hundred and twelve consecutive procedures involving autologous iliac-crest bone graft were performed, from December 29, 1992, to July 1, 1993, following a traumatic injury of the spine in 108 patients. Sixty of the sites from which the bone graft had been obtained were drained with a single large Hemovac device. The drains were maintained for two to five days postoperatively. The remaining fifty-two incisions were closed without a drainage device. All patients were evaluated clinically for problems with wound-healing. The incisions were considered to be healed when they had been asymptomatic for one year. Of eleven patients who had problems with wound-healing, six had been managed with a drain and five had not. The findings of this study do not support the routine use of drainage at the donor sites of iliac-crest bone grafts.