Ras mediates translation initiation factor 4E-induced malignant transformation.

Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras.     

Monoclonal antibodies OKT 11 and OKT 11A have pan-T reactivity and block sheep erythrocyte “receptors”

Monoclonal antibodies OKT11 (γ1) and OKT11A (γ2) are described and appear to have similar binding specificities. They bind, in immunofluorescence, with >95% of infant thymocytes, staining both cortical and medullary cells, 65-80% of blood lymphocytes and selectively stain the T cell-dependent paracortical areas of tonsil. A small proportion (9-12%) of bone marrow lymphocytes stain, but this population excludes the terminal transferase-positive cells. Both the γ1 and γ2 antibodies stain the surface membrane Ig-negative lymphocytes in blood and tonsil and are able to block sheep E rosette formation (to normal or leukemic T cells). In contrast, other monoclonal anti-T reagents tested (OKT1, OKT3, OKT4, OKT6, OKT8, OKT9, OKT10) did not block E rosette formation. E rosette formation and OKT11 binding are coincident on T-ALL cell lines and both are trypsin-sensitive. In a series of 145 leukemias and 26 leukemic cell lines investigated, only leukemias with a T cell phenotype including E rosette positivity were reactive with OKT11 and OKT11A. OKT11A binds to a polypeptide of approximately 50000 molecular weight on thymic lymphocytes. This structure may carry the recognition site for sheep erythrocytes. These antibodies provide additional useful markers for T cell analysis and are of potential therapeutic value.     

海绵质骨螺旋钉拔出试验之生物力学分析

评估螺旋钉设计优劣的简便方法之一为拔出试验。虽然比较用之海绵质骨试件可取自相同部位，自同一方向植入螺旋钉，并具有相同基准。然而因各处海绵质骨骼结构不尽相同，至今尚未有人探讨如使用不同之海绵质骨结构，例如近似等向性之杆状结构，或是板与杆组合之有强列方向排列者，对于螺旋钉拔出之最大力量有多大影响？采用牛股骨远端部位及牛颈椎Ｃ２～Ｃ６作为不同结构特性之试体。并各由两相互垂直之方向旋入螺旋钉，来做拔出试验。最后并建立一三维有限元素模型，用以研究螺纹周围之变形模式及其预测拔出最大力量的准确性。模型分析中以应变能密度准则作为破坏之参考标准。     

Expression of glycine receptors in rat sensory neurons vs. HEK293 cells yields different functional properties

In neurodegenerative diseases, such as Alzheimer's disease or HIV encephalitis, neuronal DNA fragmentation has been observed at unexpected high frequencies, without definitive evidence for activation of an irreversible apoptotic pathway. The wobbler mouse is a suggested genetic model of neurodegenerative disease. The mutant mouse develops normally until the fourth week of age when atrophy and weakness of forelimb muscles become apparent. There is a slow progression of the disease and wobbler mice may survive for several months. Spinal cord examination reveals the presence of several motoneurons with perikaryal vacuolar degeneration. In this study, we observed, using terminal dUTP nick-end-labelling staining in mutant spinal cord sections, a massive although very transient DNA fragmentation in different cell types, including glial cells and motoneurons, before the apparition of any clinical symptoms. In older wobbler mice, this DNA fragmentation had completely disappeared and the majority of motoneurons survived. To our knowledge, this is the first example of a massive and transient DNA fragmentation in the central nervous system during the early course of a neurodegenerative disease.     

Management of steroid-induced osteoporosis

Purpose To review the pathogenesis, clinical presentation, diagnostic assessment and treatment regimens of steroid-induced bone loss. Data sources An English-language literature search (MEDLINE 1966-1999) and bibliographic reviews of textbooks and review articles. Study selection Cross-sectional and prospective studies with BMD measurements or fracture rate. Results The greatest rate of bone loss occur during the first 6 to 12 months of steroid therapy, affecting trabecular more than cortical bone. High steroid dosage for a prolonged period, prevalent fracture, hypogonadism, older age, low calcium intake and family history of osteoporosis are risk factors for steroid-induced bone loss. Based on bone density results, patients with osteoporosis or osteopenia with a T-score below -1.5 should receive antiresorptive treatment during steroid therapy. Among the various antiresorptive agents, bisphosphonates have the strongest evidence of preventing steroid-induced bone loss. Conclusion The most important step in the management of steroid-induced osteoporosis is the proper assessment of the individual patient’s risk of bone loss, and the selection of appropriate anti-resorptive agent for each patient.     

Elevated expression of ETS-1 gene in a metastatic, tumorigenic human prostate epithelial cell line transformed by the v-Ki-ras oncogene

We investigated the inhibitory effects of intrasplenic combination therapy with OK-432 and recombinant interleukin-2 (IL-2) on liver metastasis of colorectal carcinoma. Intrasplenic administration group significantly inhibited the development of liver metastasis compared with subcutaneous administration group (p<0.05). Combination therapy significantly inhibited the development of subclinical liver metastasis compared with that in the control group. Combination therapy decreased the percentage of cells expressing CD8a, which may be a part of effective factors of combination therapy, and improved overall survival rate. These findings suggested intrasplenic combination therapy with OK-432 and IL-2 might be effective in inhibiting liver metastasis of colorectal carcinoma.     

Factors associated with analgesic and psychotropic medications use by community-dwelling older people with chronic pain

OBJECTIVE: The present study sought to examine use prevalence and factors associated with use of analgesic and psychotropic medications in community-dwelling older people with chronic non-malignant pain. METHOD: The study group comprised 193 community-dwelling older people with daily chronic non-malignant pain who were selected from a random sample of 1,000 older people in Melbourne. RESULTS: The use prevalence for the study group was 63% for analgesics and 39% for psychotropic medications, which is higher than the general older population without chronic pain (p < 0.00001). More women with chronic pain used analgesics, while psycho-social factors such as problems with sleeping and living at home alone were found to be associated with an increased use of psychotropic medications. CONCLUSION: A high proportion of community-dwelling older people with chronic non-malignant pain use analgesic and psychotropic medications. IMPLICATIONS: These findings provide the basis for further investigation into the level and appropriateness of analgesic and psychotropic medication use by older people with chronic pain.     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999