DNA methylation changes in human lung epithelia cells exposed to multi-walled carbon nanotubes

Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO₂NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO₂NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome.     

Flow-cytometric DNA analysis as a means for early detection of malignancy in patients with chronic ulcerative colitis.

A new approach to the problem of monitoring patients with chronic ulcerative colitis is presented and discussed in connection with a case report. When annual colonoscopies are performed, biopsies are taken for histopathological examination and DNA measurements are made using flow-cytometric techniques (FCM). Using the latter approach, gross chromosomal aberrations indicating malignant transformation in a cell population may be detected. In a 46 year old man with a long history of ulcerative colitis, an area with slight mucosal dysplasia at light microscopy was accompanied by two aneuploid cells lines - that is, colonic mucosa cells with an abnormal amount of DNA in the nuclei. An operation one year later revealed a 5 X 2 mm large adenocarcinoma in the corresponding area of the colon. We suggest that flow-cytometric techniques can be used as a complement to already practised methods for monitoring the colorectal mucosa in colitic patients for the early detection of malignancy.     

Interaction between human polymorphonuclear leukocytes and Streptococcus milleri group bacteria.

Because Streptococcus milleri group (SMG) bacteria--Streptococcus constellatus, Streptococcus intermedius, and Streptococcus anginosus--exhibit a striking propensity to cause abscesses, the interaction of these organisms with human polymorphonuclear leukocytes (PMNL) was examined. After incubation in pooled normal human serum, SMG stimulated less chemotaxis than did Staphylococcus aureus, in contrast to viridans streptococci, which caused greater chemotaxis than did S. aureus. PMNL ingested greater numbers of SMG and viridans streptococci than S. aureus but killed these organisms more slowly and less completely. Relative resistance to killing by PMNL is expected in organisms that cause abscesses, and inhibition of chemotaxis may contribute to pathogenicity, because delayed arrival of PMNL gives a head start to proliferating bacteria. This study helps explain the capacity of SMG to cause abscesses. It is unclear, however, why viridans streptococci, bacteria that rarely produce abscesses, share some of these same properties.     

Minimally invasive surgical implantation of left ventricular epicardial leads for ventricular resynchronization using video-assisted thoracoscopy

BACKGROUND AND OBJECTIVES: Cardiac resynchronization via left ventricular or biventricular pacing is an option for selected patients with ventricular systolic dysfunction and widened QRS complex. Stimulation through a coronary vein is the technique of choice for left ventricular pacing, but this approach results in a failure rate of approximately 8%. We describe our initial experience with minimally invasive surgical implantation of left ventricular epicardial leads using video-assisted thoracoscopy. PATIENTS AND METHOD: A total of 14 patients with congestive heart failure, NYHA functional class 3.2 (0.6) and mean ejection fraction 22.9 (6.8)% were included in this study. Left bundle branch block, QRS complex >140 ms and abnormal septal motion were observed in all cases. Epicardial leads were implanted on the left ventricular free wall under general anesthesia using video-assisted thoracoscopic surgery. RESULTS: Lead implantation was successful in 13 patients. Conversion to a small thoracotomy was necessary in one patient. All patients were extubated in the operating room. None of the patients died during their hospital stay. Follow-up showed reversal of ventricular asynchrony and significant improvement in ejection fraction and functional class. CONCLUSIONS: Minimally invasive surgery for ventricular resynchronization using video-assisted thoracoscopy in selected patients is a safe procedure that makes it possible to choose the best site for lead implantation and provides adequate short- and medium-term stimulation.     

Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Cardiac Aspergillosis with pedunculated mass in the left ventricle

Immunosuppression can allow organisms that are not usually pathogenetic to cause disease; under such circumstances, Aspergillus species frequently form large masses of fungal elements. We describe the case of a 12-year-old girl with hematologic remission of leukemia. She had a left ventricular pedunculated mass that was detected by echocardiographic study; at surgery, the presence of Aspergillus terreus was confirmed.