Tumors and inflammatory infiltrates: friends or foes?

The recognition of a role for inflammation in the natural history of a tumor has a long record, stretching from the mid-19th century. From the times of Virkow, who postulated that cancer originates from inflamed tissues, to Metchnikoff and many others, this field has continued to excite (and divide) the scientific community. The question as to whether the inflammatory infiltrate helps or hinders tumors is still open. In a sense, modern molecular biology has, if anything, worsened this dualism, and the literature on this issue shows a plethora of conflicting reports. We would like to provide another contribution to this topic, which was the subject of a recent brilliant review (Balkwill F and Mantovani A. Lancet 2001; 357: 539–45 [1]), by focussing more specifically to the relation between inflammation and tumor invasion and how this could drive rational therapeutic approaches. This revised version was published online in July 2006 with corrections to the Cover Date.     

Validation of a Novel Surgical Data Capturing System Following Total Hip Arthroplasty

Background

The OrthoMiDaS (Orthopedic Minimal Data Set) Episode of Care (OME) database was developed in an effort to advance orthopedic outcome measurements on a national scale. This study was designed to evaluate if the OME data capture system would increase the quality of data collected in the context of primary and revision total hip arthroplasty (THA) compared to conventional operative notes.

Birmingham hip resurfacing versus cementless total hip arthroplasty in patients 55 years or younger: A minimum five-year follow-up

Objective

The optimal reconstructive method for advanced degenerative hip disease in young adults is a topic of ongoing discussion. The purpose of this study is to report the largest single institution experience from the United States on the outcomes of Birmingham hip resurfacing (BHR) vs. cementless total hip arthroplasty (THA) in patients 55 years or younger at a minimum follow-up of five years. Currently, BHR is the only FDA-approved hip resurfacing implant available in the US.

A pyrosequencing assay for the quantitative methylation analysis of the PCDHB gene cluster, the major factor in neuroblastoma methylator phenotype

Epigenetic alterations are hallmarks of cancer and powerful biomarkers, whose clinical utilization is made difficult by the absence of standardization and of common methods of data interpretation. The coordinate methylation of many loci in cancer is defined as 'CpG island methylator phenotype' (CIMP) and identifies clinically distinct groups of patients. In neuroblastoma (NB), CIMP is defined by a methylation signature, which includes different loci, but its predictive power on outcome is entirely recapitulated by the PCDHB cluster only. We have developed a robust and cost-effective pyrosequencing-based assay that could facilitate the clinical application of CIMP in NB. This assay permits the unbiased simultaneous amplification and sequencing of 17 out of 19 genes of the PCDHB cluster for quantitative methylation analysis, taking into account all the sequence variations. As some of these variations were at CpG doublets, we bypassed the data interpretation conducted by the methylation analysis software to assign the corrected methylation value at these sites. The final result of the assay is the mean methylation level of 17 gene fragments in the protocadherin B cluster (PCDHB) cluster. We have utilized this assay to compare the methylation levels of the PCDHB cluster between high-risk and very low-risk NB patients, confirming the predictive value of CIMP. Our results demonstrate that the pyrosequencing-based assay herein described is a powerful instrument for the analysis of this gene cluster that may simplify the data comparison between different laboratories and, in perspective, could facilitate its clinical application. Furthermore, our results demonstrate that, in principle, pyrosequencing can be efficiently utilized for the methylation analysis of gene clusters with high internal homologies.     

Detection of Epstein-Barr virus genomes by in situ DNA hybridization with a terminally biotin-labeled synthetic oligonucleotide probe from the EBV Not I and Pst I tandem repeat regions

We describe a case of acute, disseminated Epstein-Barr virus (EBV) infection which was analyzed for the cellular distribution of viral replication by automated, colorimetric in situ DNA hybridization using a single, synthetic, terminally biotin-labeled oligonucleotide probe composed of 23 consecutive nucleotides selected from the EBV Not I region. The GC-rich, Not I region is a 125-base pair sequence that is repeated in tandem an average of 12.6 times in the EBV genome. The synthetic sequence had 91% base homology with another EBV genomic tandem repeat, the 102-base pair Pst I region, which is also GC-rich, has an overall 70% homology with the Not I region, and is reiterated about 25 times in the viral DNA. Disseminated EBV infection was detected in nuclei of atypical lymphocytes in several organs, including lung, bronchus, trachea, spleen, liver, and stomach, with the probes. In addition, the synthetic oligomer compared favorably with a significantly more expensive, nick translated, biotinylated probe cloned from the BAM HI-V (W), large internal repeat region. This 3.0-kilobase pair (kbp) sequence is repeated an average of 11 times in EBV. Although both probes identified regions repeated multiple times in the virus, and each confirmed an identical tissue distribution for the infection, the signal obtained with the Not I/Pst I probe was more intense and confined to the nuclei of fewer lymphocytes than the general, more weakly distributed signal obtained with the probe from the large internal repeat region. Consistent positive cellular staining was obtained with the Not I/Pst I probe in both EBV-infected control tissue culture cells and in formalin-fixed, paraffin-embedded tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Birmingham Hip Resurfacing in Patients 55 Years or Younger: Risk Factors for Poor Midterm Outcomes

Background

Birmingham hip resurfacing (BHR) is the only Food and Drug Administration–approved hip resurfacing system available in the United States and is used as an alternative to conventional total hip arthroplasty in younger patients. The purpose of this study is to report on the midterm outcomes of BHR in patients 55 years and younger, and specifically to examine the risk factors for aseptic failure, all-cause revision, and complications in this patient population.

Analysis of Epstein-Barr virus in hodgkin's disease: Experience of a single university hospital in Korea

Hodgkin's disease is known to be associated with Epstein-Barr virus (EBV) infection in Western countries, and viral nucleic acids and proteins have been identified within Reed-Sternberg (RS) cells, which are the histopathologic hallmark of the disease process. Twenty-five cases of Hodgkin's disease from a single university hospital in Korea were studied for evidence of EBV by in situ hybridization for EBV DNA and RNA and immunohistochemistry for an EBV latent protein. EBV nucleic acids were studied by a rapid (60 minutes) in situ hybridization procedure, which utilized biotinylated DNA probes specific for the following nucleic acid sequences: (1) EBV EBER1 RNA (an abundant RNA sequence expressed during latent EBV infection), (2) EBV Notl repeats (a tandemly repeated DNA sequence, which has been established to identify amplified EBV genome in lytic EBV infection), and (3) BAM HI W (a DNA sequence reiterated 11 times within the viral genome). In addition, immunohistochemistry for EBV latent membrane protein, a protein that is capable of inducing cellular transformation in cell culture, was also performed. EBV was identified within the neoplastic RS cells by at least one method in 19/25 cases (76%). The mixed cellularity subtype was the most common subtype associated with EBV infection (11/13–85%). In situ hybridization for EBV EBER1 RNA was the most sensitive method for EBV detection and was present in 17/25 cases. A significant proportion of Korean Hodgkin's disease cases is associated with EBV infection. © 1994 Wiley-Liss, Inc.     

Induction of apoptosis by fenretinide in tumor cell lines correlates with DLX2, DLX3 and DLX4 gene expression

We investigated a possible relationship between apoptosis induction by fenretinide (4HPR) and the expression of a group of genes thought to be essential in morphogenesis and development, the DLX genes. We analyzed their expression under normal conditions or upon 4HPR stimulation in several tumor cell lines. We show that DLX2, DLX3 and DLX4 were expressed at higher levels in cell lines which where more sensitive to apoptotic induction, whereas DLX 5 and 6 appeared to segregate in a distinct functional compartment. Our data support the notion that DLX2, 3, 4 genes could participate in the control of 4HPR-mediated apoptosis, making them important molecules for the monitoring of therapy efficacy in cancer patients.     

Novel homozygous TSFM pathogenic variant associated with encephalocardiomyopathy with sensorineural hearing loss and peculiar neuroradiologic findings

neurogenetics - TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible...