Radio-oncologic therapeutic strategy in curative treatment of non-small-cell bronchial carcinoma

Radiotherapy is an important modality in the postoperative and primary treatment of non-small cell lung cancer. Treatment results are rather unsatisfactory and have not basically changed in the past 15-20 years. In the nearer past, new treatment strategies were developed, which may contribute to a substantial improvement of the poor prognosis. On one hand, novel fractionation schedules using hyperfractionated accelerated radiation show promising results by improving local control. On the other hand, the main interest of many groups is focussed on a combined modality treatment using radiotherapy plus neoadjuvant or concurrent chemotherapy and surgery. There are numerous reports in the literature which document an advantage in survival of combined modalities over radiotherapy alone with improvements concerning local control as well as distant spread. The bases of the encouraging results is the use of a simultaneous or sequential combination of cisplatin-containing chemotherapy and high dose radiation. The following article reviews the relevant data from the literature with main emphasis on radiochemotherapy regimens.     

Fluorescence flow cytometry of human leukocytes in the detection of LDL receptor defects in the differential diagnosis of hypercholesterolemia

A flow-cytometric method with fluorescence-labeled monoclonal antibodies (MABs) against the low density lipoprotein (LDL) receptor (C7A MAB) or 3,3'-dioctadecylindocarbocyanin-iodide (DiI) LDL has been developed that allows the quantification of LDL receptors on leukocytes and the identification of patients with familial hypercholesterolemia (FH) within 48 hours. Leukocytes were isolated from 10 mL anticoagulated blood by density gradient centrifugation. To induce maximal expression of LDL receptors, mononuclear cells were preincubated with either phytohemagglutinine (PHA) or lipoprotein-deficient serum (LPDS). LPDS-treated monocytes provided a more homogeneous cell population with regard to LDL receptor activity than did the PHA-treated lymphocytes; they also provided a greater discrimination between the fluorescence of the receptor probes and cellular autofluorescence. The C7A MAB was able to compete for DiI LDL binding by about 40%. In competition with unlabeled LDL, DiI LDL revealed linear binding, indicating an affinity similar to native LDL. The binding characteristics of DiI LDL were also similar to 125I-LDL binding. LDL isolated from familial defective apolipoprotein B-100 was not able to compete for DiI LDL binding on monocytes, whereas native LDL reduced it by about 80%. In monocytes from FH heterozygous patients, the cellular mean fluorescence using either C7A MAB or DiI LDL at 4 degrees C was 30% to 70%; in FH homozygotes, cellular mean fluorescence was less than 20% of that in monocytes from normal individuals. In patients with familial defective apolipoprotein B-100 antibody binding was normal, but one patient's own LDL failed to compete with normal DiI LDL for 4 degrees C binding on U937 test monocytes. Patient monocytes having internalization defects showed normal 4 degrees C DiI LDL binding, but at 20 degrees C cell-associated fluorescence was reduced by about 40%. In our study 384 hypercholesterolemic patients (preselected according to serum cholesterol levels, clinical symptoms, and family history) were analyzed for LDL receptor expression using the C7A MAB-based assay. In 71.8% of the patients with cholesterol levels higher than 300 mg/dL, an LDL receptor deficiency was observed. Apolipoprotein E isoforms and lipoprotein[a] were found to be independent from the LDL receptor status. In some patients with high cholesterol levels but normal LDL receptor expression with the C7A MAB assay, LDL receptor defects could be diagnosed when either reduced binding or internalization of DiI LDL or familial defective apolipoprotein B-100 was detected.(ABSTRACT TRUNCATED AT 400 WORDS)     

"Multiple inference-inviting properties" of interpersonal verbs: Event instigation, dispositional inference, and implicit causality.

The properties of interpersonal verbs (e.g., help, dislike, etc.) that systematically influence "implicit causality" are analyzed in 3 studies. It is argued that interpersonal verbs have a set of properties (multiple inference-inviting properties [MIIPs]) that are differentially elicited as a function of the type of property primed by the type of inference request. Study 1 distinguishes event instigation as a property that is systematically influenced by verb type: Action verbs induce subject inferences, and state verbs induce object inferences. Study 2 shows that dispositional inferences are mainly mediated by action verbs and the referentiality (sentence subject or object) of adjectives that are morphologically derived from verbs. Study 3 shows that studies of implicit causality have confounded event instigation and dispositional inferences in their operationalizations and Study 3 suggests that inferences of dispositionality and event instigation are orthogonal factors contributing differentially to what has to date been referred to as "implicit causality." The implications of these findings are discussed in terms of the interface between language and social cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of cysteine residues of spinach ferredoxin-NADP+ reductase As assessed by site-directed mutagenesis

To investigate the functional role of the cysteine residues present in the spinach ferredoxin-NADP+ oxidoreductase, we individually replaced each of the five cysteine residues with serine using site-directed mutagenesis. All of the mutant reductases were correctly assembled in Escherichia coli except for the C42S mutant protein. C114S and C137S mutant enzymes apparently showed structural and kinetic properties very similar to those of the wild-type reductase. However, C272S and C132S mutations yielded enzymes with a decreased catalytic activity in the ferredoxin-dependent reaction (14 and 31% of the wild type, respectively). Whereas the C132S was fully competent in the diaphorase reaction, the C272S mutant flavoprotein showed a 35-fold reduction in catalytic efficiency with respect to the wild-type enzyme (0.4 versus 14.28 microM-1 s-1) due to a substantial decrease of kcat. NADP+ binding by the C272S mutant enzyme was apparently quantitatively the same (Kd = 37 microM) but qualitatively different, as shown by the differential spectrum. Stopped-flow experiments showed that the enzyme-FAD reduction rate was considerably decreased in the C272S mutant reductase, along with a much lower yield of the charge-transfer transient species. It is inferred from these data that the charge transfer (FAD-NADPH) between the reductase and NADPH is required for hydride transfer from the pyridine nucleotide to flavin to occur with a rate compatible with catalysis.     

The content of asbestos bodies in the bronchoalveolar fluid as a parameter of an increased pulmonary asbestos load

Pulmonary asbestos burdens are usually determined by quantitative pulmonary dust analysis. The aim of this study was to investigate the value of bronchoalveolar lavage (BAL) for this purpose. First, the upper limit of normal for asbestos bodies (AB) in BAL fluid was established using a reference group of 371 patients with no evidence of increased exposure to asbestos. 99% of these patients had less than 0.5 AB/ml. In order to see whether BAL fluid AB concentration reflected pulmonary tissue content, BAL fluid and lung tissue from a further 64 patients with diverse histories of asbestos exposure were investigated. There was a positive association between AB concentration in BAL fluid and lung tissue only for the overall group of 64 patients (r = 0.86; P < 0.001). Twelve of 13 patients with more than 1 AB/ml and ten patients with more than 5 AB/ml had more than 1000 AB/cm3 lung tissue, a value that is usually exceeded in asbestosis. When the upper concentration limit was set at 0.5 AB/ml for BAL fluid and 50 AB/cm3 for lung tissue, only two out of 64 patients had a false positive value (specificity 95%), but eleven patients had false negative results (sensitivity 58%). These investigations establish that concentrations of > or = 0.5 AB/ml are a reliable indicator of increased asbestos exposure and concentrations > 1 AB/ml are associated with a higher probability of having more than 1000 AB/cm3 lung tissue. However, exclusion of increased asbestos exposure is not possible on the basis of negative BAL findings, since the sensitivity of the method is too low.