Homozygous deletions of the p16 tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia

The p16 gene, also referred to as MTS1, INK4, CDK4I, or CDKN2, at chromosome 9p21 has recently been described as a tumor suppressor that may be involved in a wide range of tumors. We have used a semiquantitative multiplex polymerase chain reaction assay to search for deletions of the p16 gene in 34 patients with chronic myeloid leukemia in blast crisis (CML BC), 19 patients with acute lymphoblastic leukemia (ALL), and 25 patients with acute myeloid leukemia (AML). Homozygous deletions of p16 exons were found in 5 of 10 (50%) patients with CML in lymphoid BC and in 5 (26%) ALL patients, but in only 1 (2%) case with AML. No deletions were found in CML BC of nonlymphoid phenotype. Comparison of chronic phase DNA or remission DNA with acute leukemia DNA in 5 individuals showed that the p16 deletions were acquired and not inherited, directly implicating these lesions in the pathogenesis of the disease. We conclude that functional elimination of the p16 gene, or a closely mapping gene, is involved in a significant number of patients with CML in lymphoid transformation.     

Tumor necrosis factor alpha induces endothelial galactosyl transferase activity and verocytotoxin receptors. Role of specific tumor necrosis factor receptors and protein kinase C

Infections with verocytotoxin (VT) producing Escherichia coli have been strongly implicated in the epidemic form of hemolytic uremic syndrome (HUS). Endothelial damage plays a central role in the pathogenesis of HUS. In vitro studies have shown that VT can damage endothelial cells after interaction with its cellular receptor globotriaosylceramide (GbOse3cer). Cytokines, such as tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) can potentiate the toxic effect of VT by inducing a protein-synthesis dependent increase in VT receptors on endothelial cells. In this study, the mechanisms underlying the increase in endothelial VT receptors induced by TNF alpha were studied in more detail. To investigate which proteins were involved in this induction, endothelial cells were incubated with and without TNF alpha in the presence of 14C-galactose or 14C-glucose. Thin-layer chromatography (TLC) analysis of the glycolipid extracts of these cells demonstrated a markedly enhanced incorporation of 14C-galactose in GbOse3cer and other galactose-containing glycolipids, suggesting that TNF alpha enhanced galactosyl-transferase activity. To examine the role of the two recently cloned TNF-receptors (TNFR-p75 and TNFR-p55) in the TNF alpha-induced increase in GbOse3cer in human endothelial cells, cells were incubated with TNF alpha, the TNFR-p55 selective R32W-S86T- TNF alpha-mutant, or the TNFR-p75 selective D143N-A145R-TNF alpha- mutant. The effect of TNF alpha activation, determined by binding- experiments with 125I-VT-1, could be largely, but not completely mimicked by R32W-S86T-TNF alpha. Although incubation of cells with D143N-A145R-TNF alpha did not show an increase in VT-1 binding, the monoclonal antibody utr-1, which prevents binding to TNFR-p75, decreased the TNF alpha-induced VT-1 binding. Activation of protein kinase C (PKC) by phorbol ester increases the expression of VT-1 receptors; this effect was prevented by the PKC inhibitor Ro31-8220 and by homologous desensitization by pretreatment with phorbol ester. In contrast, the presence of the protein kinase inhibitor Ro31-8220 or desensitization of PKC activity reduced the TNF alpha-induced increase in VT-1 receptors maximally by 50% and 24%, respectively. Comparable reductions in overall protein synthesis and the synthesis of E-selectin and plasminogen activator inhibitor-1 (PAI-1) were observed. This suggests an effect on general protein synthesis rather than a specific effect of PKC in the signal transduction pathway, by which TNF alpha induces VT-1 receptors. Our results indicate that TNF alpha can increase the VT-1 receptors on endothelial cells by inducing galactosyl- transferase activity, that this action of TNF alpha mainly occurs via the TNFR-p55; and that PKC activation increases expression of VT-1 receptors by a separate mechanism that acts additively to the TNF alpha- induced increase in VT-1 receptors.     

A novel MIS technique for posterior cruciate ligament avulsion fractures

Objective

Open surgical approaches to treat tibial avulsion fractures of the posterior cruciate ligament (PCL) often use large incisions involving extensive muscle dissection and retraction. The objective of this study was to describe a new mini-invasive approach targeting the fractured zone, to minimize surgical dissection and improve recovery and rehabilitation.

Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease

A group of 1,390 asymptomatic men screened for latent coronary artery disease by maximal treadmill testing and double Master two-step test were followed up for a mean of 6.3 years. Angina, sudden death or acute myocardial infarction was used as the end point for coronary heart disease. There were differences in testing sensitivity and specificity among age and subject groups, but maximal treadmill testing out-performed the double Master test as a screening technique. Maximal treadmill testing demonstrated a 60.9 percent sensitivity, 92 percent specificity and a 20 percent probability that coronary artery disease would develop in a subject with an abnormal response. A risk ratio of 14.3 was obtained and demonstrated that maximal treadmill testing was a valuable screening technique for latent coronary artery disease. However, limitations of the sensitivity and specificity of the functional S-T segment response were apparent. The abnormal S-T segment response to exercise testing did not absolutely predict the future presentation of coronary artery disease, and a normal response to maximal treadmill testing did not rule out this possibility. Because premature ventricular contractions demonstrated a very low sensitivity, predictive value and risk ratio they were not a practical indicator of increased risk for latent coronary artery disease except when associated with an abnormal S-T segment response.     

血管紧张素受体抑制剂：可降低老年痴呆发病率

本研究的目的是探讨血管紧张素受体抑制剂能否预防阿尔茨海默病和痴呆,或者减缓这两种疾病的病情进展。     

A retrospective analysis of the accuracy of T2-weighted images and dynamic gadolinium-enhanced sequences in the detection and characterization of focal hepatic lesions

The aim of this study was to determine the relative ability of T2-weighted and dynamic gadolinium-enhanced T1-weighted gradient-echo sequences to detect and characterize focal hepatic lesions. We retrospectively studied 37 patients with proven focal hepatic lesions using the following sequences: a T1-weighted spin-echo sequence (T1), a T2-weighted sequence (T2), and a series of breath-hold dynamic gadolinium-enhanced T1-weighted gradient-echo sequences (Gd). Two observers were asked to determine retrospectively the number and type of focal hepatic lesions present using images from three combinations of sequences (T1+T2, T1+Gd, T1+T2+Gd). Proof of the number and diagnosis of focal lesions in each patient was established using a consensus read. Both readers detected more focal lesions when both the T2-weighted sequences and the gadolinium-enhanced sequences were available than on either sequence alone, although this improvement reached statistical significance (P<0.05) only for one of the readers. There was no significant difference (P<0.05) in the ability to characterize lesions between any of the sets of sequences. The combination of dynamic gadolinium-enhanced images and T2-weighted images was shown to assess focal hepatic lesions better than either of these sequences alone.