Epistemic community formation: a bibliometric study of recurring authors in medical journals

Scientometrics - Using a selection of general science journals, general medical journals and specialized medical journals, this paper analyses four indicators of epistemic community formation:...     

Carcinoembryonic antigen in diagnosis and monitoring of colorectal cancer]

Female SJL mice are more susceptible than male mice to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP)-specific T lymphocytes. In the present study, we examined mechanisms involved in this gender-related difference in disease susceptibility. MBP-specific T lymphocytes derived from spleens of males during the effector phase of adoptive EAE produced significantly higher levels of IL-10, an anti-inflammatory cytokine in EAE. A protective effect of testosterone was then shown. Females implanted with dihydrotestosterone pellets demonstrated a significantly less severe course of EAE as compared with females implanted with placebo pellets. Finally, MBP-specific T lymphocytes derived from dihydrotestosterone-implanted females produced significantly higher levels of IL-10 than those from placebo. Together these data indicate that testosterone exerts a protective effect in EAE that is mediated at least in part by enhanced production of IL-10 by autoantigen-specific T lymphocytes.     

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis

Antibiotic treatment options for Burkholderia cepacia infection are limited because of high intrinsic resistance. The problem is complicated by development of cross-resistance between antibiotics of different classes. We isolated antibiotic-resistant mutants by stepwise exposure to chloramphenicol (Chlor) and to trimethoprim/sulphamethoxazole (T/S) for four B. cepacia strains: ATCC13945, Per (clinical isolate), Cas and D4 (environmental isolates). Chlor(r) mutants did not produce chloramphenicol acetyl-transferase. Cross-resistance, defined as greater than four-fold increase in MIC by microtitre dilution method, was consistently seen in both types of mutants. For chloramphenicol-resistant (Chlor[r]) and trimethoprim/sulphamethoxazole-resistant (Tr/Sr) mutants of B. cepacia ATCC13945 and Cas, no MIC change was seen for piperacillin, ceftazidime, rifampicin, gentamicin, tobramycin, polymyxin B or azithromycin. B. cepacia-Per and -D4 mutants showed cross-resistance to ceftazidime and to piperacillin. Comparison of outer membrane protein (OMP) profiles of B. cepacia and their mutants by SDS-PAGE revealed Tr/Sr) mutants to be deficient in a major OMP (molecular weight 39-47 kDa). Tr/Sr mutants also expressed additional OMPs not found in wild type strains at 75-77 kDa for B. cepacia-ATCC13945 and -Cas, and 20-21 kDa in B. cepacia-D4 and -Per. No OMP changes occurred in Chlor(r) mutants. Lipopolysaccharide (LPS) profiles of each type of mutant showed new high and low molecular weight LPS bands. Cross-resistance seems to be mediated by alterations in porin and LPS for Tr/Sr mutants, but only by LPS in Chlor(r) mutants.     

Indicators for inspection and maintenance planning of concrete structures

Based on an idea introduced by Benjamin and Cornell (1970. Probability, statistics and decision for civil engineers. New York: McGaw Hill) and previous works by the authors it is demonstrated how condition indicators may be formulated for the general purpose of quality control and for assessment and inspection planning in particular. The formulation facilitates quality control based on sampling of indirect information about the condition of the considered components. This allows for a Bayesian formulation of the indicators whereby the experience and expertise of the inspection personnel may be fully utilized and consistently updated as frequentistic information is collected. The approach is illustrated on an example considering a concrete structure subject to corrosion. It is shown how half-cell potential measurements may be utilized to update the probability of excessive repair after 50 years. Furthermore in the same example it is shown how the concept of condition indicators might be applied to develop a cost optimal maintenance strategy composed of preventive and corrective repair measures.     

Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature

Cerebral hemodynamic changes in infants with progressive hydrocephalus have been studied with the transcranial Doppler (TCD) technique. Several authors have referred to the correlation between the hemodynamic changes and increased intracranial pressure (ICP). Despite conflicting conclusions on the value of pulsatility index (PI) and resistance index (RI) measurements for monitoring infantile hydrocephalus, these pulsatility indices are the most commonly used for this purpose. Although clinical signs of raised ICP are highly variable and unreliable in infants, assumptions have been made in most of the studies about the presence of elevated ICP on the basis of the patient's clinical state. Few studies have reported on actual ICP values, however, and a direct relationship between ICP and TCD changes has never been adequately demonstrated. In the present study, this relationship was investigated in long-term simultaneous TCD/ICP measurements, in an attempt to develop a noninvasive method of monitoring the effect of ICP on intracranial hemodynamics. Two groups of data sets were established. Group I consisted of pre- and postoperative (shunt implantation) TCD/ICP measurements. Group II were long-term simultaneous TCD/ICP recordings showing significant ICP variations. In most of the postoperative measurements there was a decrease in the average PI and RI values. The correlation between PI or RI and ICP in the long-term simultaneous recordings, however, was generally poor. The risk of obtaining false positive or false negative PI or RI values in short-term measurements was also demonstrated. It can be concluded from our results, besides the wide range of reference values for the Doppler indices and extracranial influences upon them, that the present Doppler indices are inadequate for monitoring the complex intracranial dynamic responses in patients with raised ICP.     

Substrate-induced conformational change in a trimeric ornithine transcarbamoylase

The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides new insights into the linkages between substrate binding, protein-protein interactions, and conformational change. The structure was solved by molecular replacement with the Pseudomonas aeruginosa catabolic OTCase catalytic trimer (Villeret, V., Tricot, C., Stalon, V. & Dideberg, O. (1995) Proc. Natl. Acad. Sci. USA 92, 10762-10766; Protein Data Bank reference pdb 1otc) as the model and refined to a crystallographic R value of 21.3%. Each polypeptide chain folds into two domains, a carbamoyl phosphate binding domain and an L-ornithine binding domain. The bound inhibitor interacts with the side chains and/or backbone atoms of Lys-53, Ser-55, Thr-56, Arg-57, Thr-58, Arg-106, His-133, Asn-167, Asp-231, Met-236, Leu-274, Arg-319 as well as Gln-82 and Lys-86 from an adjacent chain. Comparison with the unligated P. aeruginosa catabolic OTCase structure indicates that binding of the substrate analog results in closure of the two domains of each chain. As in E. coli aspartate transcarbamoylase, the 240s loop undergoes the largest conformational change upon substrate binding. The clinical implications for human OTCase deficiency are discussed.     

Enhancing effect of natural killer cell stimulatory factor (NKSF/interleukin-12) on cell-mediated cytotoxicity against tumor-derived and virus-infected cells

Natural killer cell stimulatory factor (NKSF) or interleukin-12 (IL-12) is a heterodimeric cytokine with pleiomorphic effects on T and NK cells, including induction of lymphokine production, mitogenesis, and enhancement of spontaneous cytotoxic activity. Similarly to IL-2, NKSF/IL-12 enhances NK cell-mediated cytotoxicity within a few hours and independently from induced proliferation. This effect is independent from other induced cytokines, because it is not prevented by antibodies neutralizing interferon (IFN)-alpha, IFN-beta, IFN-gamma, IL-2 or tumor necrosis factor (TNF)-alpha and, unlike the induction of IFN-gamma production by peripheral blood lymphocytes, it does not require HLA class II-positive accessory cells. Enhanced cytotoxicity is accompanied by morphologic changes in NK cells, including a significant increase in the number of cytoplasmic granules. In addition to the previously described ability to enhance the cytotoxic activity of NK cells against tumor-derived target cells, NKSF/IL-12 is also a potent stimulator of cytotoxicity against virus-infected cells, either fibroblasts acutely infected with herpes viruses or T cell lines chronically infected with human immunodeficiency virus-1. NK cell-mediated antibody-dependent cytotoxicity or anti-CD16 antibody-redirected lysis is not significantly enhanced by NKSF/IL-12. However, the ability of resting peripheral blood T cells to mediate anti-CD3 antibody-redirected lysis is enhanced by 18-h incubation with NKSF/IL-12, indicating that this lymphokine can modulate the cytotoxic capability of both NK and T cells.