High-resolution HLA typing for the DQB1 gene by sequence-based typing

BACKGROUND: Monocytic tissue factor (TF), initiating the extrinsic blood coagulation pathway, is often upregulated under septic or inflammatory conditions. The complex activating mechanism remains largely unclear and no effective strategy has been firmly established. In this study, we used a model monocytic cell line (human leukemic THP-1 promonocytes) to address (1) the nature of TF activation in response to bacterial endotoxin and (2) the application of anti-inflammatory cytokines in relieving monocytic hypercoagulation. RESULTS: TF in THP-1 cells was substantially activated by exposure to bacterial endotoxin (LPS; 5 micrograms/ml) for 6 h. Human recombinant IL-4 (500 ng/ml) and IL-10 (500 ng/ml) inhibited TF activation induced by LPS. To determine if these cytokines depressed LPS recognition resulting in such inhibition, we employed an anti-CD14 mAb (UCHM-1; Sigma Chemical) to address the role of CD14 in LPS transmembrane signaling. LPS-induced TF activation was depressed by 35% upon inclusion of the anti-CD14 mAb (1:10 dilution). This antibody alone mimicked TF activation which accounted for 35% of the LPS-induced TF activation, suggesting the activating role of CD14 ligation. In addition, the anti-CD14 mAb elicited the production of nitric oxide (NO) which was found to be independent of TF activation. NO production could serve as an independent index for monitoring LPS recognition. IL-4 depressed the anti-CD14 mAb-induced TF activation as well as NO elicitation, indicating the blockade of CD14 ligation. In contrast, IL-10 showed differential inhibitory activities. TF activation induced by either LPS or anti-CD14 mAb was inhibited by IL-10 which did not show any inhibition on NO elicitation under these conditions. In a separate approach, neither IL-4 nor IL-10 inhibited phorbol ester-induced NO elicitation. More direct evidence came from an epifluorescent demonstration showing that IL-4 blocked binding of FITC-conjugated LPS and anti-CD14 mAb to THP-1 cells. CONCLUSIONS: Taken together, the results suggest that LPS action in relation to TF activation consists of CD14-independent and -dependent signaling including CD14 ligation. We also showed that anti-inflammatory cytokines (IL-4 and -10) significantly depressed TF activation. IL-4 antagonized CD14-dependent LPS recognition leading to the depression in TF activation.     

p-aminohippurate uptake by syncytial microvillous membrane vesicles of human term placenta

The mechanism of uptake of p-aminohippurate (PAH) by syncytial microvillous membrane vesicles of human term placenta was investigated. Initial PAH uptake and efflux were increased in the presence of a pH-gradient and a Cl(-)-gradient, respectively. Forced negative and positive membrane potentials did not influence the uptake, which indicated that the transport is not electrogenic. The pH-dependent increase is probably the result of a higher rate of diffusion due to a lower degree of dissociation of PAH. Because several organic anions failed to transstimulate PAH uptake and FCCP did not decrease the uptake in the presence of an inwardly directed H(+)-gradient, ruling out a PAH/OH- antiport, an anion exchange system does not appear to be present in these membranes. Since electrogenicity and anion exchange seem not to be involved in the Cl(-)-dependent increase, an allosteric effect of Cl- on the transporter might be possible. Various organic anions were able to inhibit pH-stimulated PAH uptake significantly. Kinetic analysis of the probenecid sensitive part of uptake provided further evidence for mediated transport of PAH (Km = 7.4 +/- 2.6 mM and Vmax = 2.0 +/- 0.4 nmol/mg/15 s). Non-inhibitable diffusion accounted for the main part of total transport. Concentration dependent inhibition of PAH transport by probenecid showed a Ki of 2.5 +/- 0.9 mM. It is concluded that human placental syncytial microvillous membrane vesicles possess a low affinity transport mechanism for PAH with low specificity. The importance of this system, for placental excretion of anionic drugs, will depend on the intrasyncytial concentration of these drugs, caused by the transport across the basal membrane.     

Clinically significant hearing loss in renal allograft recipients treated with intravenous erythromycin

BACKGROUND: Hearing loss is generally regarded as a rare side effect of erythromycin therapy. However, our own clinical experiences in erythromycin-treated patients led us to suspect that this complication may be more common among renal allograft recipients. The purpose of this study was to evaluate the incidence, predisposing factors, clinical characteristics, and outcomes of erythromycin-induced hearing loss among renal allograft recipients. METHODS: We reviewed medical records of renal transplant patients treated for pneumonia with intravenous erythromycin lactobionate. Patients were evaluated for the occurrence of clinically significant hearing loss (including onset, duration, and reversibility), other signs and symptoms of ototoxicity (vertigo and tinnitus), daily erythromycin dose and duration of treatment, concurrent ototoxic drug therapy, renal and hepatic function, and history of previous otic disease. RESULTS: Eleven (32%) of 34 courses of intravenous erythromycin therapy resulted in hearing loss. The incidence of hearing loss was 53% (eight of 15 courses) in patients treated with 4 g of erythromycin daily compared with 16% (three of 19 courses) among those receiving 2 g/d (P = .05). In addition, courses of erythromycin were longer in those suffering auditory toxicity (9.6 +/- 4.7 days) than in nontoxic patients (5.7 +/- 3.6 days) (P < .05). Hepatic and renal function did not differ between toxic and nontoxic patients. All episodes of erythromycin-induced hearing loss were reversible. CONCLUSIONS: We conclude that clinically significant hearing loss occurs in more than 30% of renal allograft recipients treated for pneumonia with intravenous erythromycin lactobionate. Patients who require prolonged courses of erythromycin and those treated with 4 g/d are at particular risk for the development of auditory toxicity. With prompt recognition and modification of therapy, erythromycin-induced hearing loss appears to be completely reversible.     

Minimum spanning trees made easier via multi-objective optimization

Many real-world problems are multi-objective optimization problems and evolutionary algorithms are quite successful on such problems. Since the task is to compute or approximate the Pareto front, multi-objective optimization problems are considered as more difficult than single-objective problems. One should not forget that the fitness vector with respect to more than one objective contains more information that in principle can direct the search of evolutionary algorithms. Therefore, it is possible that a single-objective problem can be solved more efficiently via a generalized multi-objective model of the problem. That this is indeed the case is proved by investigating the computation of minimum spanning trees.This work was supported by the Deutsche Forschungsgemeinschaft (DFG) as part of the Collaborative Research Center Computational Intelligence (SFB 531) and by the German-Israeli Foundation (GIF) in the project Robustness Aspects of Algorithms.     

The Role of Acceptance and Job Control in Mental Health, Job Satisfaction, and Work Performance.

Acceptance, the willingness to experience thoughts, feelings, and physiological sensations without having to control them or let them determine one's actions, is a major individual determinant of mental health and behavioral effectiveness in a more recent theory of psychopathology. This 2-wave panel study examined the ability of acceptance also to explain mental health, job satisfaction, and performance in the work domain. The authors hypothesized that acceptance would predict these 3 outcomes 1 year later in a sample of customer service center workers in the United Kingdom (N = 412). Results indicated that acceptance predicted mental health and an objective measure of performance over and above job control, negative affectivity, and locus of control. These beneficial effects of having more job control were enhanced when people had higher levels of acceptance. The authors discuss the theoretical and practical relevance of this individual characteristic to occupational health and performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Criteria to disprove context freeness of collage languages

Collage grammars are context-free devices which generate picture languages consisting of collages—sets of parts, where a part is a set of points in a given space. In order to show that certain collage languages cannot be generated, the well-known pumping technique turns out to be rather useless. To circumvent this difficulty, other necessary criteria for context-freeness are established in this paper. Roughly speaking, these criteria reveal that (1) the collages in a context-free collage language can be deflated stepwise in such a manner that the difference between subsequent collages in the resulting chain is small and (2) the volume of parts can grow or shrink only exponentially.     

Respiratory complications following tonsillectomy/UPPP: is step-down monitoring necessary?

We conducted a study to determine if the risk of airway compromise following tonsillectomy with uvulopalatopharyngoplasty justifies the added cost and inconvenience of step-down monitoring in an intensive care unit. We performed a retrospective chart review of 130 patients with obstructive sleep apnea who had undergone isolated tonsillectomy with uvulopalatopharyngoplasty at our tertiary care center. The average length of stay in the step-down unit was 18 hours. We found that only eight of these patients (6.2%) had a postoperative desaturation level of less than 90%, including three of 12 patients (25%) who had comorbid conditions. No patient had an adverse respiratory event. We conclude that step-down monitoring in an intensive care unit is not necessary, although caution should be exercised in monitoring patients with comorbidities because they appear to be more prone to desaturation. A complete lack of adverse respiratory events has not been reported in previous studies.