Mouse deformed epidermal autoregulatory factor 1 recruits a LIM domain factor, LMO-4, and CLIM coregulators

Nuclear LIM domains interact with a family of coregulators referred to as Clim/Ldb/Nli. Although one family member, Clim-2/Ldb-1/Nli, is highly expressed in epidermal keratinocytes, no nuclear LIM domain factor is known to be expressed in epidermis. Therefore, we used the conserved LIM-interaction domain of Clim coregulators to screen for LIM domain factors in adult and embryonic mouse skin expression libraries and isolated a factor that is highly homologous to the previously described LIM-only proteins LMO-1, -2, and -3. This factor, referred to as LMO-4, is expressed in overlapping manner with Clim-2 in epidermis and in several other regions, including epithelial cells of the gastrointestinal, respiratory and genitourinary tracts, developing cartilage, pituitary gland, and discrete regions of the central and peripheral nervous system. Like LMO-2, LMO-4 interacts strongly with Clim factors via its LIM domain. Because LMO/Clim complexes are thought to regulate gene expression by associating with DNA-binding proteins, we used LMO-4 as a bait to screen for such DNA-binding proteins in epidermis and isolated the mouse homologue of Drosophila Deformed epidermal autoregulatory factor 1 (DEAF-1), a DNA-binding protein that interacts with regulatory sequences first described in the Deformed epidermal autoregulatory element. The interaction between LMO-4 and mouse DEAF-1 maps to a proline-rich C-terminal domain of mouse DEAF-1, distinct from the helix-loop-helix and GATA domains previously shown to interact with LMOs, thus defining an additional LIM-interacting domain.     

Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.     

Variations of cardiac cycle length in patients with coronary heart disease before and after aortic coronary bypass surgery

It is well known that variations in cardiac cycle length or heart rates may be used for noninvasive evaluation of autonomic cardiovascular control. The investigation uses an original procedure. The data for analysis of cardiac cycle length variations (CCLV) are those obtained regularly at follow-up intervals, random 24-hour Holter 2-lead ECG recordings for 5 sec, and simultaneously calculated continuous sequence of mean heart rate. With the procedure, the correlations of CCLV with the parameters reflecting the early postoperative status of patients with CHD, including acute myocardial infarction, acute heart failure, rhythm and conduction disturbances, as well as age, operative stress, concurrent diseases. The findings are of both diagnostic and predictive value at subsequent stages of CHD treatment.     

A histomorphological study in age related changes in the elastic fiber system of the basilar artery

The aim of the study was to quantify the distribution of elastic fibers within the wall of the basilar artery. Three age groups were studied: 1) 0-1 yr.; 2) 20-50 yr. 3) > 50 yr. A histomorphometrical study was undertaken using an estimation of the linear density of the components of the fibrous elastic tissue system: the full length in the proximal and distal segments of the basilar artery was evaluated. Our results showed that: The elastic tissue of the basilar artery is not evenly distributed throughout the tunica media. Compared to the 0 to 1-year age group, mature elastic, elauninic and oxytalan fibers decreased with age. In all age groups the linear density of the mature elastic fibers was more evident in the proximal than in the distal segment of the artery.     

Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis

BACKGROUND: The course of tissue changes in acute myocarditis in humans is not well understood. Diagnostic tools currently available are unsatisfactory. We tested the hypothesis that inflammation is reflected by signal changes in contrast-enhanced magnetic resonance imaging (MRI). METHODS AND RESULTS: We assessed 44 consecutive patients with symptoms of acute myocarditis. Nineteen patients met the inclusion criteria revealing ECG changes, reduced myocardial function, elevated creatine kinase, positive troponin T, serological evidence for acute viral infection, exclusion of coronary heart disease, and positive antimyosin scintigraphy. We studied these patients on days 2, 7, 14, 28, and 84 after the onset of symptoms. We obtained ECG-triggered, T1-weighted images before and after application of 0.1 mmol/kg gadolinium. We measured the global relative signal enhancement of the left ventricular myocardium related to skeletal muscle and compared it with measurements in 18 volunteers. The global relative enhancement was higher in patients on days 2 (4.8+/-0.3 [mean+/-SE] versus 2.5+/-0.2; P<.0001); 7 (4.7+/-0.5, P<.0001); 14 (4.6+/-0.5, P<.0002); and 28 (3.9+/-0.4, P=.009) but not on day 84 (3.1+/-0.3; P=NS). On day 2, the enhancement was focal, whereas at later time points, the enhancement was diffuse. In patients with evidence of ongoing disease, the values remained elevated. CONCLUSIONS: Acute myocarditis evolves from a focal to a disseminated process during the first 2 weeks after onset of symptoms. Contrast media-enhanced MRI visualizes the localization, activity, and extent of inflammation and may serve as a powerful noninvasive diagnostic tool in acute myocarditis.     

Quorum sensing in Escherichia coli and Salmonella typhimurium

Escherichia coli and Salmonella typhimurium strains grown in Luria-Bertani medium containing glucose secrete a small soluble heat labile organic molecule that is involved in intercellular communication. The factor is not produced when the strains are grown in Luria-Bertani medium in the absence of glucose. Maximal secretion of the substance occurs in midexponential phase, and the extracellular activity is degraded as the glucose is depleted from the medium or by the onset of stationary phase. Destruction of the signaling molecule in stationary phase indicates that, in contrast to other quorum-sensing systems, quorum sensing in E. coli and S. typhimurium is critical for regulating behavior in the prestationary phase of growth. Our results further suggest that the signaling factor produced by E. coli and S. typhimurium is used to communicate both the cell density and the metabolic potential of the environment. Several laboratory and clinical strains of E. coli and S. typhimurium were screened for production of the signaling molecule, and most strains make it under conditions similar to those shown here for E. coli AB1157 and S. typhimurium LT2. However, we also show that E. coli strain DH5alpha does not make the soluble factor, indicating that this highly domesticated strain has lost the gene(s) or biosynthetic machinery necessary to produce the signaling substance. Implications for the involvement of quorum sensing in pathogenesis are discussed.     

Helicobacter pylori infection: prevalence and clinical relevance in a large company

Although gastrointestinal (GI) illnesses account for considerable sick absenteeism, there have been few workplace studies of GI disorders. We determined the prevalence of Helicobacter pylori infection by serology and assessed its relation to upper GI tract complaints, personal ulcer history, and family history of stomach cancer in 6,143 employees (mean age, 40.4 years) at BASF's main chemical production facilities in Ludwigshafen, Germany. Employees were recruited during occupational health clinic visits (n = 4,488) and through broad communications efforts (n = 1,655). Participation among clinic attendees was 66%, and this recruitment method was particularly effective in reaching shift employees. Positive immunoglobulin G (IgG) serology (38.2%), ulcers (4.9%), nonulcer dyspepsia (20.4%), and a family history of stomach cancer (6.1%) were common occurrences in this work setting. Further diagnostic evaluation and eradication therapy was recommended for 795 employees (12.9%), based on a combination of positive serology and either upper GI tract complaints or family stomach cancer history, and has been completed for 541 employees. A weak but consistent association was seen between positive serology and cigarette smoking, and shift work was found to be associated with positive serology, but not with ulcer or nonulcer dyspepsia occurrence.