Higher frequency of chromosomal aberrations in ovarian endometriosis compared to extragonadal endometriosis: A possible link to endometrioid adenocarcinoma

Endometriosis may progress to invasive endometrioid adenocarcinoma, particularly in the ovary. Up to now, little is known of the molecular mechanisms possibly involved in the malignant transformation of endometriosis. Therefore, in this study, extragonadal endometriosis (n = 10), ovarian endometriosis without malignancy (n = 10), ovarian endometriosis with direct transition into endometrioid adenocarcinoma (n = 8), and normal endometrium (n = 12) were investigated for numerical chromosomal aberrations by fluorescence in situ hybridization using centromere enumeration probes. The proportions of cells with aneusomies were semiquantitatively assessed. Trisomies 1 and 7, and monosomies 9 and 17 were found in endometriosis, ovarian endometrioid adenocarcinoma, and normal endometrium. The proportions of aneusomic cells were significantly higher in ovarian endometrioid carcinoma compared with ovarian endometriosis (P < 0.001), and in ovarian endometriosis compared with extragonadal endometriosis and normal endometrium (P < 0.001). The data provide new evidence of a common lineage of endometriosis and ovarian endometrioid carcinoma. The higher frequency of chromosomal aberrations in endometrioid carcinoma than in endometriosis may reflect an expansion of aberrant cell clones already present in endometriosis during the progression to cancer. The higher frequency of chromosomal aberrations in ovarian endometriosis than in extragonadal endometriosis suggests a role of the ovarian stromal milieu in the induction of genetic changes, which may eventually lead to invasive cancer.

Increased genome instability in Escherichia coli lon mutants: relation to emergence of multiple-antibiotic-resistant (Mar) mutants caused by insertion sequence elements and large tandem genomic amplifications

Thirteen spontaneous multiple-antibiotic-resistant (Mar) mutants of Escherichia coli AG100 were isolated on Luria-Bertani (LB) agar in the presence of tetracycline (4 microg/ml). The phenotype was linked to insertion sequence (IS) insertions in marR or acrR or unstable large tandem genomic amplifications which included acrAB and which were bordered by IS3 or IS5 sequences. Five different lon mutations, not related to the Mar phenotype, were also found in 12 of the 13 mutants. Under specific selective conditions, most drug-resistant mutants appearing late on the selective plates evolved from a subpopulation of AG100 with lon mutations. That the lon locus was involved in the evolution to low levels of multidrug resistance was supported by the following findings: (i) AG100 grown in LB broth had an important spontaneous subpopulation (about 3.7x10(-4)) of lon::IS186 mutants, (ii) new lon mutants appeared during the selection on antibiotic-containing agar plates, (iii) lon mutants could slowly grow in the presence of low amounts (about 2x MIC of the wild type) of chloramphenicol or tetracycline, and (iv) a lon mutation conferred a mutator phenotype which increased IS transposition and genome rearrangements. The association between lon mutations and mutations causing the Mar phenotype was dependent on the medium (LB versus MacConkey medium) and the antibiotic used for the selection. A previously reported unstable amplifiable high-level resistance observed after the prolonged growth of Mar mutants in a low concentration of tetracycline or chloramphenicol can be explained by genomic amplification.

Polymorphism and chromosomal location of the MC4R (melanocortin-4 receptor) gene in the dog and red fox

The melanocortin-4 receptor (MC4R) is expressed in the hypothalamus and regulates energy intake and body weight. In silico screening of the canine chromosome 1 sequence and a comparison with the porcine MC4R sequence by BLAST were performed. The nucleotide sequence of the whole coding region and 3'- and 5'-flanking regions of the dog (1214 bp) and red fox (1177 bp) MC4R gene was established and high conservation of the nucleotide sequences was revealed (99%). Five sets of PCR primers were designed and a search for polymorphism was performed by the SSCP technique in a group of 31 dogs representing nineteen breeds and 35 farm red foxes. Sequencing of DNA fragments, representing the identified SSCP patterns, revealed three single nucleotide polymorphisms (including a missense one) in dogs and four silent SNPs in red foxes. An average SNP frequency was approx. 1/400 bp in the dog and 1/300 bp in the red fox. We mapped the MC4R gene by FISH to the canine chromosome 1 (CFA1q1.1) and to the red fox chromosome 5 (VVU5p1.2).

State affective instability in borderline personality disorder assessed by ambulatory monitoring

BACKGROUND: Although affective instability is an essential criterion for borderline personality disorder (BPD), it has rarely been reported as an outcome criterion. To date, most of the studies assessing state affective instability in BPD using paper-pencil diaries did not find indications of this characteristic, whereas in others studies, the findings were conflicting. Furthermore, the pattern of instability that characterizes BPD has not yet been identified. METHOD: We assessed the affective states of 50 female patients with BPD and 50 female healthy controls (HC) during 24 hours of their everyday life using electronic diaries. RESULTS: In contrast to previous paper-and-pencil diary studies, heightened affective instability for both emotional valence and distress was clearly exhibited in the BPD group but not in the HC group. Inconsistencies in previous papers can be explained by the methods used to calculate instability (see Appendix). In additional, we were able to identify a group-specific pattern of instability in the BPD group characterized by sudden large decreases from positive mood states. Furthermore, 48% of the declines from a very positive mood state in BPD were so large that they reached a negative mood state. This was the case in only 9% of the HC group, suggesting that BPD patients, on average, take less time to fluctuate from a very positive mood state to a negative mood state. CONCLUSION: Future ambulatory monitoring studies will be useful in clarifying which events lead to the reported, sudden decrease in positive mood in BPD patients.

Traumatische chronische Instabilität des proximalen Tibiofibulargelenkes [Traumatic chronic instability of the proximal tibiofibular joint]

The rare condition of chronic instability of the proximal tibiofibular joint can be of traumatic or idiopathic origin and can lead to secondary arthritis. After conservative treatment for 6 months and persistent pain, operative treatment should be considered. We present a case of traumatic instability, ligament reconstruction with a part of the biceps femoris tendon, and postoperative return to full and painless sport activities.

Imaging structural abnormalities in the hip joint: instability and impingement as a cause of osteoarthritis

Osteoarthritis is thought to be caused by a combination of intrinsic vulnerabilities of the joint, such as anatomic shape and alignment, and environmental factors, such as body weight, injury, and overuse. It has been postulated that much of osteoarthritis is due to anatomic deformities. Advances in surgical techniques such as the periacetabular osteotomy, safe surgical dislocation of the hip, and hip arthroscopy have provided us with effective and safe tools to correct these anatomical problems. The limiting factor in treatment outcome in many mechanically compromised hips is the degree of cartilage damage which has occurred prior to treatment. In this regard, the role of imaging, utilizing plain radiographs in conjunction with magnetic resonance imaging, is becoming vitally important for the detection of these anatomic deformities and pre-radiographic arthritis. In this article, we will outline the plain radiographic features of hip deformities that can cause instability or impingement. Additionally, we will illustrate the use of MRI imaging to detect subtle anatomic abnormalities, as well as the use of biochemical imaging techniques such as dGEMRIC to guide clinical decision making.

Sarcoid-derived fibroblasts: links between genomic instability, energy metabolism and senescence.

Bovine papillomavirus 1 (BPV-1) is a well recognized etiopathogenetic factor in a cancer-like state in horses, namely equine sarcoid disease. Nevertheless, little is known about BPV-1-mediated cell transforming effects. It was shown that BPV-1 triggers genomic instability through DNA hypomethylation and oxidative stress. In the present study, we further characterized BPV-1-positive fibroblasts derived from sarcoid tumors. The focus was on cancer-like features of sarcoid-derived fibroblasts, including cell cycle perturbation, comprehensive DNA damage analysis, end-replication problem, energy metabolism and oncogene-induced premature senescence. The S phase of the cell cycle, polyploidy events, DNA double strand breaks (DSBs) and DNA single strand breaks (SSBs) were increased in BPV-1-positive cells compared to control fibroblasts. BPV-1-mediated oxidative stress may contribute to telomere dysfunction in sarcoid-derived fibroblasts. Loss of mitochondrial membrane potential and concurrent elevation in intracellular ATP production may be a consequence of changes in energy-supplying pathways in BPV-1-positive cells which is also typical for cancer cells. Shifts in energy metabolism may support rapid proliferation in cells infected by BPV-1. Nevertheless, sarcoid-derived fibroblasts representing a heterogeneous cell fraction vary in some aspects of metabolic phenotype due to a dual role of BPV-1 in cell transformation and oncogene-induced premature senescence. This was shown with increased senescence-associated β-galactosidase (SA-β-gal) activity. Taken together, metabolic phenotypes in sarcoid-derived fibroblasts are plastic, which are similar to greater plasticity of cancer tissues than normal tissues.