Estimation of Disease Prevalence from a Screening Program

The estimation problem of disease prevalence from a screening program is considered. Due to the imperfect nature of a screening test, the estimate should be adjusted based upon the sensitivity and the specificity of the screening test. Several approximate methods of constructing the confidence interval of prevalence are given and the score method is proposed in detail. A simulation study is also presented and discussed.     

popharvest: An R package to assess the sustainability of harvesting regimes of bird populations

Bird harvest for recreational purposes or as a source for food is an important activity worldwide. Assessing or mitigating the impact of these additional sources of mortality on bird populations is therefore crucial issue. The sustainability of harvest levels is however rarely documented, because knowledge of their population dynamics remains rudimentary for many bird species. Some helpful approaches using limited demographic data can be used to provide initial assessment of the sustainable use of harvested bird populations, and help adjusting harvest levels accordingly. The Demographic Invariant Method (DIM) is used to detect overharvesting. In complement, the Potential Take Level (PTL) approach may allow setting a level of take with regard to management objectives and/or to assess whether current harvest levels meet these objectives. Here, we present the R package popharvest that implements these two approaches in a simple and straightforward way. The package provides users with a set of flexible functions whose arguments can be adapted to existing knowledge about population dynamics. Also, popharvest enables users to test scenarios or propagate uncertainty in demographic parameters to the assessment of sustainability through easily programming Monte Carlo simulations. The simplicity of the package makes it a useful toolbox for wildlife managers or policymakers. This paper provides them with backgrounds about the DIM and PTL approaches and illustrates the use of popharvest''s functionalities in this context.     

Multigeneration exposure test of Drosophila melanogaster to ELF magnetic fields

Mutations, other than dominant lethals, were accumulated on wild type second chromosomes (+) of Drosophila melanogaster during exposure to 50 Hz sinusoidal alternating magnetic fields of 0.5 or 5 mT (rms) for 40 generations by the Curly/Plum(Cy/Pm) accumulation method. We maintained, for 40 generations under continuous exposure, each (+) chromosome as a heterozygote with (Cy) chromosome. Viability of the (+) chromosome was tested by sib-mating of (Cy/+) male and (Cy/+) female in a culture every 10th generation to obtain the homozygote. Viability indices, defined as twice the ratio of number of (+/+) flies to that of (Cy/+) flies plus 1 in the progeny of the test mating, also were calculated, which equaled 1.00 at the starting point. For the control and 0.5 and 5 mT exposed groups, percent frequencies of recessive lethal lines, defined as a line with (+/+) flies less than 0.3% in the test mating, were, respectively, 1.9, 0.9, and 2.9% (10th), 9.0, 4.9, and 9.5% (20th), 30.3, 22.9, and 30.4% (30th), and 39.9, 32.4, and 43.3% (40th generation). For the control and 0.5 and 5 mT groups, average viability indices, excluding lethals and markedly deleterious, were, respectively, 0.778, 0.796, and 0.752 (20th), 0.704, 0.698, and 0.694 (30th), and 0.669, 0.678, and 0.595 (40th generation). Their decreasing rates were 0.0054, 0.0059, and 0.0078 per generation. No significant difference was detected among the exposure levels in either the recessive lethal mutation frequency or the viability index. Bioelectromagnetics 19:335–340, 1998. © 1998 Wiley-Liss, Inc.     

Determination of drug levels in human serum by circular dichroism

A study of the applicability of circular dichroism (CD) for the determination of drug levels in human serum is described and a new method for the quantitative determination of optically active absorbing drugs having Cotton effects at wavelengths above 250 nm in human serum and/or plasma is proposed. The principal advantages of this method are speed, economy, and simplicity, no derivatization or chromatographic separation steps being needed. The validity of the CD determination was confirmed by analysis of variance, β-lactam antibiotics being chosen as model drugs. In addition, the validation studies performed confirm the accuracy and precision of the proposed method. For β-lactam antibiotics lacking Cotton effects above 250 nm, an alternative method based on the extraction of the drug from serum is considered. Chirality 10:507–512, 1998. © 1998 Wiley-Liss, Inc.     

Similarity between nuclear matrix proteins of various cells revealed by an improved isolation method

Comparative analysis of nuclear matrix proteins by two-dimensional electrophoresis may be greatly impaired by copurifying cytoskeletal proteins. The present data show that the bulk of adhering cytofilaments may mechanically be removed by shearing of nuclei pretreated with vanadyl ribonucleoside complexes. Potential mechanisms of action not based on ribonuclease inhibition are discussed. To individually preserve the integrity of nuclear structures, we developed protocols for the preparation of nuclear matrices from three categories of cells, namely leukocytes, cultured cells, and tissue cells. As exemplified with material from human lymphocytes, cultured amniotic cells, and liver tissue cells, the resulting patterns of nuclear matrix proteins appeared quite similar. Approximately 300 spots were shared among the cell types. Forty-nine of these were identified, 21 comprising heterogeneous nuclear ribonucleoproteins. Heterogeneous nuclear ribonucleoproteins L and nuclear lamin B2 isoforms were identified by amino acid sequencing and mass spectrometry. However, individually expressed proteins, such as the proliferating cell nuclear antigen, also pertained following application of the protocols. Thus, enhanced resolution and comparability of proteins improve systematic analyses of nuclear matrix proteins from various cellular sources. J. Cell. Biochem. 71:363–374, 1998. © 1998 Wiley-Liss, Inc.     

Enantioselective determination of isradipine in human serum using chiral stationary phase liquid chromatography and gas chromatography with nitrogen selective detection

rac-Isradipine is a dihydropyridine type calcium antagonist. Its calcium entry blocking effect is due primarily to the (+)-(S)-enantiomer. This study describes a sensitive enantioselective method for the determination of isradipine in human serum. Following alkaline extraction into hexane, the enantiomers of isradipine are separated quantitatively by high-performance liquid chromatography on a Chiralcel OJ column at 39°C. The collected fractions were evaporated and assayed using capillary gas chromatography on a HP 50+ column with nitrogen selective detection. Using 2.0 ml of serum, 0.7 nmol/1 (0.26 ng/ml) of each enantiomer could be determined with acceptable precision. The method has successfully been used to measure (+)-(S)- and (−)-(R)-isradipine concentrations in samples from volunteers after intravenous and oral administration of isradipine. Chirality 10:808–812, 1998. © 1998 Wiley-Liss, Inc.     

A new method for modeling large-scale rearrangements of protein domains

A method for modeling large-scale rearrangements of protein domains connected by a single- or a double-stranded linker is proposed. Multidomain proteins may undergo substantial domain displacements, while their intradomain structure remains essentially unchanged. The method allows automatic identification of an interdomain linker and builds an all-atom model of a protein structure in internal coordinates. Torsion angles belonging to the interdomain linkers and side chains potentially able to form domain interfaces are set free while all remaining torsions, bond lengths, and bond angles are fixed. Large-scale sampling of the reduced torsion conformational subspace is effected with the “biased probability Monte Carlo-minimization” method [Abagyan, R.A., Totrov, M.M. (1994): J. Mol. Biol. 235, 983–1002]. Solvation and side-chain entropic contributions are added to the energy function. A special procedure has been developed to generate concerted deformations of a double-stranded interdomain linker in such a way that the polypeptide chain continuity is preserved. The method was tested on Bence-Jones protein with a single-stranded linker and lysine/arginine/ornithine-binding (LAO) protein with a double-stranded linker. For each protein, structurally diverse low-energy conformations with ideal covalent geometry were generated, and an overlap between two sets of conformations generated starting from the crystallographically determined “closed” and “open” forms was found. One of the low-energy conformations generated in a run starting from the LAO “closed” form was only 2.2 Å away from the structure of the “open” form. The method can be useful in predicting the scope of possible domain rearrangements of a multidomain protein. Proteins 27:410–424, 1997. © 1997 Wiley-Liss, Inc.     

Reversible binding interactions between the tryptophan enantiomers and albumins of different animal species as determined by novel high performance liquid chromatographic methods: an attempt to localize the D- and L-tryptophan binding sites on the human serum albumin polypeptide chain by using protein fragments

The stereoselectivity of the reversible binding interactions between the D- and L-tryptophan enantiomers and serum albumins of different animal species and fragments of human serum albumin (HSA) was investigated by applying three novel high performance liquid chromatographic (HPLC) arrangements. The separations were performed by means of (1) an achiral (diol-bond), (2) a chiral (bovine serum albumin-bond) silica gel sorbent, and (3) a column switching technique which uses both the diol- and HSA-bond HPLC stationary phases. A polarimetric detector and/or an ultraviolet (UV) spectrophotometer were used to monitor the separation process. HPLC arrangement 3 allowed the evaluation of enantioselective binding for D- and L-tryptophan to different albumins and albumin fragments. At present, column switching can be considered the technique of the broadest applicability for investigating the reversible binding interactions between a protein and drug enantiomers. Chirality 9:373–379, 1997. © 1997 Wiley-Liss, Inc.     

粪便学在有蹄类动物数量调查研究中的应用与展望

随着与分子生物学的结合,传统的粪便学不仅拓宽了在种群生态学、行为生态学及保护遗传学等研究时取样的范围,而且能提供更多的有效信息,使得传统的粪便计数方法得以在新的领域里发展。本文对传统粪便学在有蹄类动物数量研究中的应用加以总结,并结合国内外研究现状对分子粪便学在这一领域内的可靠性、局限性及应用前景做了概述。