Antibodies to heteromeric glycolipid complexes in multifocal motor neuropathy.

BACKGROUND: Measurement of anti-GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies react to heteromeric complexes of two or more glycolipids, are being increasingly applied to this area of diagnostic testing. METHODS: A newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme-linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes. RESULTS: By ELISA, 22/33 MMN cases had detectable anti-GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti-GM1 antibodies by glycoarray. Analysis of variance (anova) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycoarray. Receiver operator characteristic analysis revealed insignificantly different diagnostic performance between the two methods. However, the glycoarray appeared to offer slightly improved sensitivity by identifying antibodies in four ELISA-negative samples. CONCLUSIONS: The use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti-glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening.

Inflammatory mediator patterns in tracheal aspirate and their association with bronchopulmonary dysplasia in very low birth weight neonates.

OBJECTIVE: Alterations in inflammatory mediators are an important finding in neonates who develop bronchopulmonary dysplasia (BPD); however, there is a lack of research examining the relationship between multiple inflammatory mediators in premature neonates and the development of BPD. This study investigated whether the distribution of 12 inflammatory mediators detected in the tracheal aspirate (TA) of neonates within 24 h of birth could differentiate between neonates who did and who did not develop BPD. STUDY DESIGN: TA samples were collected from 27 very low birth weight neonates (BPD+=11), and the concentrations of 12 biomarkers associated with BPD were determined. Linear discriminant analysis (LDA) was used to classify neonates into two outcome groups. RESULT: LDA based on the 12 measured biomarkers displayed a significant level of discriminant function (P=0.007). CONCLUSION: Using linear discriminant analysis, predictive models of BPD can be generated. Our results suggest that multiple inflammatory mediators collected within 24 h of birth may be used to classify neonates into who will and who will not develop BPD.

Glucose-induced modulation of nutrient influx in Schistosoma mansoni.

The tegumental influx of adenine, adenosine, arginine, choline, histidine, and lysine has been measured in mated and separated male and female Schistosoma mansoni 7-10 wk postinfection. Tissue uptake indices were measured after a brief rinse in either 5 mM glucose or glucose-free saline. Data indicate that schistosomes respond rapidly to this 2-3-sec exposure to glucose-free medium, and lowered uptake rates are observed. Similar studies, measuring cytosine and lysine uptake in Schistosoma japonicum indicate that, in this species also, reduced nutrient influx is seen after a transient exposure to glucose-free medium. It is proposed that these metabolites are not taken up by active transport processes, but rather the effect observed is the consequence of a rapid change in glucose metabolism.

In pursuit of commitment. Hiring executives who share the ministry's values.

A major concern for religious-sponsored healthcare facilities is securing top administrative personnel who are both professionally competent and committed to the religious institute's mission. One process to identify such individuals involves defining the organization's priorities; establishing a search committee; assessing value-oriented credentials; and selecting the value-driven executive. Identifying persons who share the organization's values is a two-part process involving the résumé and the formal interview. The Résumé Evaluation Form attempts to identify a candidate's value orientation in three areas: knowledge of, experience with, and implementation of Catholic culture. The Interview Analysis Form explores other areas, such as whether the candidate speaks the organization's "language," the individual's underlying motivation for seeking employment in a Catholic organization, and what issues, projects, or concerns engender passion in the candidate. After the interview, the committee should discuss and interpret the scores and perceptions of each committee member and assign a numerical ranking for each candidate. In addition to the numerical ranking, the committee should assess the candidate's personal characteristics, values, and priorities.

Tegumental glucose permeability in male and female Schistosoma mansoni.

Tegumental hexose transporters have been kinetically characterized in mated and separated male and female Schistosoma mansoni 8-12 wk postinfection. Significant gender-specific differences in Km and Vmax were observed. In mated males, the estimated constants (mean +/- SE) were: Km = 0.63 +/- 0.31 mM, Vmax = 0.93 +/- 0.44 nmol/mg worm water/min, and the Kd = 0.25 +/- 0.09 microliter/mg worm water/min. In mated females the kinetics were: Km = 0.99 +/- 0.40 mM, Vmax = 1.22 +/- 0.42 nmol/mg worm water/min, and Kd = 0.60 +/- 0.14 microliter/mg worm water/min. The influx of 2-deoxy-D-glucose and 3-O-methylglucose has been similarly characterized; these analogs share the same glucose transporter in male and female schistosomes. 2-Deoxy-D-glucose has a higher affinity, and 3-O-methylglucose a lower affinity, than does glucose. Because mated male schistosomes supply glucose to female partners, similarities between the free glucose concentration of the male and the affinity of the transporter determined for mated female schistosomes suggest that male-to-female transfer may be a potentially rate-limiting step in glucose utilization by the female. Permeability x surface are (PS) products and Vmax/Km ratios were significantly elevated in mated schistosomes, suggesting that the transporter is primarily localized to the dorsal surface of the male. Gender- and mating-specific analyses of PS products indicate that tegumental permeability to glucose is significantly increased in mated schistosomes, and compares very favorably to that of the host liver.

Comparative glucose utilization rates in separated and mated schistosomes.

The rate of phosphorylation of 2-deoxyglucose (2DG) was determined by sequential pulsing of schistosomes (Schistosoma mansoni, S. japonicum, and S. haematobium) with 3H- and 14C-labeled 2-deoxy-D-glucose. Subsequent column chromatographic separation of the neutral [3H]2DG and [14C]2DG from the 3H- and 14C-labeled 2-deoxy-D-glucose 6-phosphate permitted estimation of the quantity of [3H]2DG phosphorylated in 2 min, and the proportion of [14C]2DG phosphorylated in 1 min; thus a phosphorylation rate was determined from a single tissue sample. The relative phosphorylation rate of 2-[3H]2DG to D-1-[14C]glucose (i.e., the phosphorylation coefficient) was also measured in male and female schistosomes. It was demonstrated that even though 2DG is taken up more rapidly than glucose, it is phosphorylated at a much slower rate in both S. mansoni and S. japonicum. In both of these species, mated males phosphorylate 2DG and glucose at a greater rate than do unmated males. Similarly, mated females phosphorylate and consume more glucose than do separated females. In contrast, the phosphorylation coefficient is greater in separated than in mated schistosomes. Intraspecific comparisons suggest that, at reduced substrate concentrations, glucose utilization rates are higher in S. japonicum, intermediate in S. mansoni, and lower in S. haematobium.

The mechanism and rate of glucose transfer from male to female schistosomes.

Short-term in vitro pulse-labeling of the free glucose pool in pairs of Schistosoma mansoni, and measurement of the increase in [14C]glucose in the female partner (and the concomitant decrease in the male), has established that glucose can be transferred from male to female schistosomes. It is demonstrated that this transfer is not inhibited by ouabain in S. mansoni. Free glucose levels have been measured in Schistosoma haematobium, Schistosoma japonicum and S. mansoni. Data indicate that the transfer of glucose is not via an active mechanism, but rather the transfer of glucose occurs along a glucose concentration gradient which exists between males and females.

Max Weber or Jesus Christ: in whose image?

The bureaucratic model of organization and the model that emerges from the Gospel and Vatican Council II provide a stark contrast for Catholic health care administrators to ponder. As articulated by sociologist Max Weber, a bureaucracy is based on a hierarchical structure with sharply defined and protected levels of authority, centralized decision making, rules that govern personnel behavior, and an impersonalized view of employees that stresses their roles as functionaries. The Christian, Gospel-based model, on the other hand, places a premium on collegiality, shared authority, the mediation of conscience, the common good, and the work of the individual. Even though only a few will shape management policy in a large hospital, policymaking should be viewed as a service, a ministry that entails stewardship. Catholic health care leaders should reflect the spirit of collegiality by bringing various strata of staff together in a dynamic, united effort. Thus the institution's statement of mission will not be an abstract recitation of pieties but a living reality, a philosophy that is "owned" by the workers.