Genetic mapping ofPim-1 putative oncogene to mouse chromosome 17

Pim-1 is a putative oncogene activated in T-cell lymphomas induced by Moloney and AKR mink cell focus forming (MCF) viruses. We have determined the chromosomal localization of the Pim-1gene in mice by Southern blot analysis of DNAs obtained from a panel of mouse-Chinese hamster somatic cell hybrids. The Pim-1gene was localized on chromosome 17, a chromosome frequently aberrant in T-cell lymphomas. Two chromosomal regions, containing sequences homologous to regions within the Pim-1locus, were localized on chromosome 6 and 16.     

Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages

Metal particles and ions from hip prostheses have the potential to induce the production of reactive oxygen species (ROS), making them prime suspects for disturbing the cellular balance of oxidants/antioxidants (redox state of the cell). To better understand the cellular effect of metal ions from metal-on-metal prostheses, the aim of this study was to examine the effect of cobalt (Co2+) and chromium (Cr3+) ions on protein oxidation in human U937 macrophages. Protein oxidation was measured by Western blot using antibodies directed against dinitrophenylhydrazine (DNP)-derivatized protein carbonyls, the most commonly measured products of protein oxidation in biological samples. Three DNP-derived proteins were detected. The first has a molecular weight of 16 kDa and is expressed at a very low level. The second has a molecular weight of 48 kDa and its level is not regulated by metal ions. The third is a 69 kDa protein and its level is regulated by Co2+ and Cr3+ ions. Therefore, the last band served as a marker of protein oxidation in the present study. Results showed that Co2+ and Cr3+ ions induced a time- and dose-dependent protein oxidation reaching 6.5 and 2.9 times the control after 72 h, respectively, which were inhibited by the antioxidant glutathione monoethyl-ester. Finally, results showed that the oxidized proteins are mainly found in the cytoplasmic fraction of the cells and are absent from the nucleus. In conclusion, our results suggest that metal ions from metal-on-metal prostheses have the potential to modify the redox state of cells both locally (periprosthetic environment) or systematically (circulating cells). The long term effect of these ions on protein oxidation in vivo remains to be investigated.     

Combination of WAGR and Potocki-Shaffer contiguous deletion syndromes in a patient with an 11p11.2-p14 deletion

Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome. The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated. We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity. She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6. This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested. Molecular and follow-up data on the original WAGRO case are briefly presented.     

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.     

Detection of Rickettsia felis in a New World flea species, Anomiopsyllus nudata (Siphonaptera: Ctenophthalmidae)

The flea and rodent samples studied in this project were collected from field study sites in New Mexico from winter 1998 to spring 2001. During this period, 155 small rodents (14 different species) were live-trapped and combed for the presence of fleas. A total of 253 fleas were collected, comprising 21 species. Two of the 253 fleas collected were polymerase chain reaction (PCR) positive for the Rickettsia 17-kDa protein gene. These two fleas were both Anomiopsyllus nudata Baker, each collected from an individual Neotoma albigula Hartley, on two occasions. Individual fleas positive for the Rickettsia 17-kDa protein gene were then tested with primers targeting the rickettsial genes for citrate synthase (gltA) and two major outer membrane proteins (ompA and ompB). The nucleotide sequences of the PCR products of these two fleas were identical to each other and were 100% (394/394), 100% (1150/1150), 99.8% (469/470), and 99.3% (818/824) similar to the corresponding sequences of the 17-kDa, gltA, ompA, and ompB genes of Rickettsia felis, respectively. Flea homogenates of individual PCR-positive fleas were inoculated into shell vials seeded with Vero cells, and the Gimenez stain technique was used to demonstrate the presence of Rickettsia-like organisms in detached cells found in aspirated medium 19 d after inoculation. These cells were harvested and tested by PCR, targeting portions of the 17-kDa and gltA genes, resulting in products 100% identical to R. felis. This work comprises the first report of R. felis detection in a flea species (A. nudata) endemic to the New World.     

Thrombus of the ascending aorta: a rare cause of myocardial infarction.

We present two cases of a thrombus in the ascending aorta causing an acute myocardial infarction (AMI) and review the 10 other cases previously reported in the literature. This life-threatening condition appears to be more common in female smokers in their fifth decade. Suspicion should be raised in individuals at low risk for atherosclerotic disease with coronary angiographic findings not in keeping with the clinical presentation. The diagnosis may be obtained by transesophageal echocardiography, and we generally recommend surgical thrombectomy.     

Breast cancer risk with postmenopausal hormonal treatment

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.     

Effects of sub-toxic concentrations of camphorquinone on cell lipid metabolism

The biological effects of camphorquinone (CQ), an initiator for light-polymerized resins, have been reported to relate to its ability to generate free radicals and cause radical-induced membrane damage via lipid peroxidation. However, the effects of CQ on lipids other than peroxidation may result in unfavorable tissue responses especially at concentrations that are not overtly toxic to cells. The purpose of the current study was to examine the effects of CQ on cell lipid metabolism at subtoxic concentrations, with or without visible light irradiation. HCP and THP-1 cells were exposed to CQ with or without light irradiation under clinically relevant conditions and lipid metabolism was analyzed using 14C-labeling and thin-layer chromatography. We found that CQ increased synthesis of neutral lipids, such as triglycerides, from 7 to nearly 15% of the total and diglycerides from 2% to about 3% of the total in HCP cells, while synthesis of phospholipids, such as sphingomyelin, was decreased by 1-1.5%. In THP-1 cells cholesterol synthesis increased more than 2-fold and cholesterol ester synthesis increased more than 5-fold. Light-activated CQ did not differ significantly in terms of its bioactivity compared to no-light conditions. We conclude that CQ significantly altered the metabolism of several important structural lipids in two cell types at sub-toxic concentrations that are clinically relevant. These changes in lipid metabolism may in turn affect membrane integrity and permeability and possibly lead to significant changes in cell responses.     

A Decline in C6 Antibody Titer Occurs in Successfully Treated Patients with Culture-Confirmed Early Localized or Early Disseminated Lyme Borreliosis

C₆, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C₆-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C₆ antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C₆ negative or had a ≥4-fold decrease in C₆ antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C₆ negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C₆ antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis.