Spectroscopic evidence for selenium(IV) dimerization in aqueous solution.

The aqueous speciation of selenium(iv) was elucidated by a combined approach applying quantum chemical calculations, infrared (IR), Raman, and (77)Se NMR spectroscopy. The dimerization of hydrogen selenite (HSeO3(-)) was confirmed at concentrations above 10 mmol L(-1) by both IR and NMR spectroscopy. Quantum chemical calculations provided the assignment of vibrational bands observed to specific molecular modes of the (HSeO3)2(2-) ion. The results presented will provide a better understanding of the chemistry of aqueous Se(iv) which is of particular interest for processes occurring at mineral/water interfaces.

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans.

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Phosphorylation and structure-based functional studies reveal a positive and a negative role for the activation loop of the c-Abl tyrosine kinase.

c-Abl is a nuclear and cytoplasmic tyrosine kinase involved in a variety of cellular growth and differentiation processes. In contrast to its oncogenic counterparts, like BCR-Abl, c-Abl is not constitutively tyrosine phosphorylated and its catalytic activity is very low. Here we report tyrosine phosphorylation of endogenous c-Abl and a concomitant increase in catalytic activity. Using Abl -/- cells reconstituted with mutated c-Abl forms, we show that phosphorylation and activity depend on Tyr412 in the activation loop. Tyr412 is also required for stimulation by PDGF or by cotransfection of active Src. Phosphorylation of Tyr412 can occur autocatalytically by a trans-mechanism and cause activation of otherwise inactive c-Abl, suggesting a positive feedback loop on c-Abl activity. In the recent structure of the Abl catalytic domain bound to the STI-571 inhibitor, unphosphorylated Tyr412 in the activation loop points inward and appears to interfere with catalysis. We mutated residues involved in stabilizing this inhibited form of the activation loop and in positioning Tyr412. These mutations resulted in tyrosine phosphorylation and activation of c-Abl, as if relieving c-Abl from inhibition. Tyr412 is therefore necessary both for activity and for regulation of c-Abl, by stabilizing the inactive or the active conformation of the enzyme in a phosphorylation-dependent manner.

[Lymph node metastases in the neck of unknown primary tumor]. / Halslymphknotenmetastasen bei unbekanntem Primärtumor.

BACKGROUND: Cervical lymph nodes represent the most frequent manifestation of lymph node metastases of unknown primary. Nearly 3% of all malignant ENT-tumors are cervical lymph nodes metastases of unknown primary. This disease is a challenge for clinical working physician in diagnosis and therapy. MATERIAL AND METHOD: In a retrospective study we investigated 99 patients with the diagnosis cervical lymph node metastases of unknown primary, which were treated and observed in our department between 1975 and 1995. Within this group we observed the course of 83 patients completely. RESULTS AND CONCLUSIONS: The tumor-dependent 5 year-survival-rate was 11%. This is very low, but similar to the literature. 40% of patients, that were operated on neck dissection with or without postoperative irradiation survived tumor-dependent 5 years. In 42 cases we could find a primary tumor. 14 of these primaries were located in the upper aero-digestive-tract, 28 in other regions of the body. The identification of the primary did not improve the prognosis of the patients. A good prognosis was associated with further occult primary, location of the lymph nodes in the upper or middle level of the neck or parotid region and a histology of squamous cell or undifferentiated carcinoma. Signs of poor prognosis were metastasis in the supraclavicular region, of adenocarcinoma and inoperability of the lymph node. The combination therapy of neck dissection and irradiation proved to be best. The extended field radiation of the complete upper aero-digestive-tract did not cause a improvement of tumor-dependent 5-year-survival. We discovered a primary in 5 of 27 patients in this group within the irradiated area. In conclusion extended field radiation must be discussed critically for patients with lymph node metastasis of unknown primary.

Crosstalk between the catalytic and regulatory domains allows bidirectional regulation of Src.

The catalytic activity of Src family tyrosine kinases is inhibited by intramolecular interactions between the regulatory SH3 and SH2 domains and the catalytic domain. In the inactive state, the critical alphaC-helix in the catalytic domain is positioned such that the formation of the Glu 310-Lys 295 salt bridge is precluded, Tyr 416 in the activation loop is unphosphorylated, and the SH2 and SH3 domains are unavailable for interactions with other proteins. We found that phosphorylation of the activation loop or mutation of the loop preceding the alphaC-helix activates Src and increases the accessibility of the SH3 domain for ligands. Interaction of the alphaC-helix with the activation loop is a central component of this regulatory system. Our data suggest a bidirectional regulation mechanism in which the regulatory domains inhibit Src activity, and Src activity controls the availability of the regulatory domains. By this mechanism, Src family kinases can be activated by proteins phosphorylating or changing the conformation of the catalytic domain. Once active, Src family kinases become less prone to regulation, implying a positive feedback loop on their activity.

A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK.

The nuclear function of the c-Abl tyrosine kinase is not well understood. In order to identify nuclear substrates of Abl, we constructed a constitutively active and nuclear form of the protein. We found that active nuclear Abl efficiently phosphorylate c-Jun, a transcription factor not previously known to be tyrosine phosphorylated. After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl. Surprisingly, elevated levels of c-Jun activated nuclear Abl, resulting in activation of the JNK serine/threonine kinase. This phosphorylation circuit generates nuclear tyrosine phosphorylation and represents a reversal of previously known signalling models.

Allograft-inflammatory factor-1 in rat experimental autoimmune encephalomyelitis, neuritis, and uveitis: expression by activated macrophages and microglial cells.

Allograft inflammatory factor-1 (AIF-1) is a Ca2+ binding peptide expressed predominantly by activated monocytes. In order to investigate the role of AIF-1 in autoimmune lesions of the rat nervous system, we have used a synthetic gene to express AIF-1 in E. coli and have produced monoclonal antibodies against AIF-1. AIF-1 was localized to monocytes/macrophages with rather selective staining of a minor rat monocyte subpopulation of lymphoid tissue. We then investigated expression of AIF-1 in experimental autoimmune encephalomyelitis (EAE), neuritis (EAN), and uveitis (EAU). Within the local inflammatory lesions, infiltrating macrophages are prominently stained. In the diseased brain, AIF-1-positive microglial cells are not only found in the direct vicinity of the infiltrate, but widespread activation is seen in the parenchyma. This is the first demonstration that AIF-1 is present in autoimmune lesions. Immunostaining of microglial cells is noteworthy, as these cells are strategically placed regulatory elements of CNS immunosurveillance. Thus, AIF-1 might be a valuable marker to dissect the local monocyte heterogeneity in autoimmune disease.

Nerve blocks for regional anesthesia of the face.

Many trauma repairs and dermatologic procedures performed on the face require anesthesia of the involved area. The specific requirements for anesthesia and vasoconstriction vary, depending on the location, size and depth of the injury or lesion. Direct infiltration of anesthetic is very uncomfortable, and adequate anesthesia may require multiple injections. In addition, direct infiltration of a volume of anesthetic sufficient to produce adequate anesthesia can cause distortion of the tissue, hindering the identification of margins. Intraoral nerve blocks routinely used by dentists can achieve safe and effective regional anesthesia in the anterior portion of the face.

Common oral conditions.

Although some oral lesions, such as torus palatinus, are normal variants, and others, such as benign migratory glossitis, are self-limited, several common oral conditions require prompt diagnosis and treatment to reduce the potential for serious complications. Treatment of dental and periodontal abscesses may include incision and drainage, antibiotic therapy, pain control and dental extraction. Treatment of sialolithiasis (blockage of the salivary gland ducts) may require application of moist heat, antibiotics and surgical removal of impacted stones. Hyperkeratosis, a white patch on the oral mucosa that does not rub off or bleed (as does the white patch of candidiasis) commonly occurs in persons who use smokeless tobacco products. The lesion may require biopsy if it still persists two to four weeks after discontinuation of the tobacco product. Squamous cell carcinoma, which accounts for 95 percent of all oral cancers and is most commonly associated with alcohol and tobacco use, is usually asymptomatic until the late stage of the disease. Suspicious lesions should be biopasied to confirm the diagnosis.

Leukocyte chemotactic factor, a natural ligand to CD4, is expressed by lymphocytes and microglial cells of the MS plaque.

The leukocyte chemotactic factor (LCF) is a proinflammatory cytokine and natural soluble ligand to the human CD4 molecule. LCF is produced by CD4+ and CD8+ T lymphocytes and is considered essential to the influx of CD4+ T lymphocytes and macrophages into an inflammatory lesion. In order to investigate the role of LCF in the multiple sclerosis (MS) lesion, we have used a synthetic gene to express LCF in E. coli and have produced monoclonal antibodies against LCF. Monoclonal antibodies are suited to demonstrate LCF in ELISAs. Western blots and paraffin-embedded tissue sections. In the MS lesion, immunopositive lymphocytes and microglial cells, notably, have been found. This is the first demonstration that LCF is present in MS lesions. Immunostaining of microglial cells is noteworthy, as these cells are strategically placed regulatory elements of CNS immunosurveillance and like other cells of the monocytic lineage express CD4 molecules. Thus, LCF might be a paracrine factor regulating T-lymphocyte chemoattraction and an autocrine molecule regulating microglial cell immune reactivity.

Air pollution measurements in traffic tunnels.

Air pollution measurements during April 1991 are reported from the Craeybeckx highway tunnel in Antwerp, Belgium. The tunnel was used daily by an average of 45,000 vehicles, of which 60% were gasoline fueled passenger cars, 20% diesel cars, and 20% trucks. Of the gasoline cars, only 3% had three-way catalysts. Tunnel air concentrations of nitrogen oxides, sulphur dioxide, carbon dioxide, carbon monoxide, nonmethane hydrocarbons, volatile organic compounds, polycyclic aromatic hydrocarbons, and lead are presented. The traffic emissions in the tunnel are calculated by the carbon balance method, which uses the increase of the total carbon concentration in the tunnel air as the reference quantity. Division of the concentration of any pollutant by the total carbon concentration gives emission factors per kilogram of carbon. These emission factors can be converted directly to emissions relative to fuel consumption or per kilometer. The fraction of diesel used in the tunnel was derived from sulphur to carbon ratios in tunnel air. A calculation procedure with breakdown of emission factors according to vehicle categories was used to estimate countrywide emissions. The estimated emissions were compared to results from the Flanders Emissions Inventory [Emissie Inventaris Vlaamse Regio (EIVR)] and calculated emissions according to the emission factors proposed by the European Commissions CORINAIR Working Group. For NOx there is excellent agreement. For carbon monoxide and hydrocarbons, the tunnel data produced higher emissions than the CORINAIR model would predict but lower than the official EIVR statistics. The estimated lead emissions from traffic are found to be 22 to 29% of the lead in gasoline.

Computer aided emergency response systems.

Over the past years several, less or more integrated emergency management support and information systems have been developed and implemented. After a short review of the larger, mainly governmentally sponsored systems and of a selection from the smaller commercially available systems, the computer aided emergency response system (CAERS) of the Belgian Nuclear Energy Research Centre is highlighted.

The role of oncogenes in cancer.

Researchers have accumulated evidence suggesting that most human cancers are the result of multiple events involving many genes functioning at various levels of expression over a long period of time. Recently, an important segment of cancer research has focused on oncogenes, a group of altered normal genes. The normal genes, known as proto-oncogenes, encode proteins necessary for the cell's structure, growth, and mitotic activity. Oncogenes have been found to be the activated forms of proto-oncogenes, which become activated as a result of point mutations, nucleotide deletions/insertions, or chromosomal translocations. Approximately 50 types of oncogenes have been discovered to date, and research had led us to believe that oncogenes are derived from normal genes that regulate growth and development. A general discussion of oncogenes will be presented in this review.

Global air quality monitoring: Trends and levels of sulphur dioxide and suspended particulate matter in selected urban areas.

An overview is presented of the development and ongoing activities of the WHO/UNEP air quality monitoring project. The project started in 1973 and is part of the Global Environmental Monitoring System. An analysis of the sulphur dioxide and suspended particulate matter is also included. The results show that the annual mean concentration for sulphur dioxide has decreased since 1973; for suspended particulate matter, however, a gradual increase is observed since 1976.

Comparison of three instrumental methods to monitor nitrogen dioxide.

Three commercially available automated NO2-monitors, based on amperometry, chemiluminescence and coulometry respectively, were compared under simulated field conditions over a period of 45 days of continuous operation. The main purpose of this programme was the study of the reliability of the overall system, sampling line-monitors-data acquisition and handling system (PDP-8/E), the correlation between the individual half-hour averages given by the three monitors in the range 0--700 mug NO2/m3 and the comparison of the global statistics for the same NO2-pollution simultaneously seen by the three different monitors over a period of 45 days. Based on more than 1200 valid half-hour averages, a highly significant correlation between the different monitors was obtained, while the statistics of the simulated NO2-pollution were in good agreement.