The presence of a dnaK (HSP70) multigene family in members of the orders Planctomycetales and Verrucomicrobiales

Sequences of the dnaK gene, coding for the 70-kDa heat shock protein (HSP70), were determined for six members of the order Planctomycetales, including representatives of three genera, and for the only cultivated member of the order Verrucomicrobiales, Verrucomicrobium spinosum. A fragment of the dnaK gene was amplified from these strains by PCR with oligonucleotide primers targeting regions of the dnaK gene that are conserved at the amino acid level, and the resulting PCR products were cloned into a plasmid vector. Sequence analysis of the cloned dnaK fragments revealed the presence of two different types of dnaK sequence in one of the planctomycete strains, Planctomyces maris, and in V. spinosum. Only one type of dnaK sequence was found for each of the remaining strains. Phylogenetic analysis of the partial sequence data suggested that the majority of planctomycete strains, including one of the Planctomyces maris sequences, form a coherent phylogenetic group branching adjacent to other main lines of descent within the domain Bacteria, as has been shown previously by 16S rRNA sequence analysis. One of the two V. spinosum dnaK sequences also appears to constitute a separate lineage within the gram-negative bacteria. Each of the remaining sequences from P. maris and V. spinosum, together with the single sequence obtained from Planctomyces limnophilus, appeared to be unrelated to the other planctomycete sequences and to occupy a position distant from that of other gram-negative bacteria. The phylogenetic diversity of dnaK sequences exhibited by P. maris and V. spinosum was comparable to that found in Synechococcus sp. strain PCC7942 and Escherichia coli, the only other prokaryotes for which a dnaK multigene family has been demonstrated.     

Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872)

MK-0991 (L-743,872) is a potent antifungal agent featuring long half-life pharmacokinetics. The pharmacokinetics of MK-0991 administered intravenously to mice, rats, rhesus monkeys, and chimpanzees is presented. Unique to MK-0991 is its consistent cross-species performance. The range of values for the pharmacokinetic parameters were as follows: clearance, 0.26 to 0.51 ml/min/kg; half-life, 5.2 to 7.6 h; and distributive volume, 0.11 to 0.27 liters/kg. The level of protein binding of MK-0991 was determined to be 96% in mouse and human serum. The compound exhibited high affinities for human serum albumin and at least two lipid components. The rationale for the selection of MK-0991 as a drug development candidate was based on its two- to threefold superior pharmacokinetic performance in chimpanzees over the performance of an otherwise equivalent analog, L-733,560. Once-daily dosing for MK-0991 is indicated by a graphical comparison of levels in the circulations of chimpanzees and mice. In a study of the pharmacokinetics of MK-0991 in mouse tissue, the organs were assayed following intraperitoneal administration. The area under the concentration-versus-time curves (AUC) segregated the tissues into three exposure categories relative to plasma. The tissues with greater exposure than that for plasma were liver (16 times), kidney (3 times), and large intestine (2 times). The exposure for small intestine, lung, and spleen were equivalent to that for plasma. Organs with lower levels of exposure were the heart (0.3 times that for plasma), thigh (0.2 times), and brain (0.06 times). Kinetically, drug was cleared more slowly from all tissues than from plasma, indicating that terminal-phase equilibrium had not been achieved by 24 h. Thus, some measure of accumulation is predicted for all tissues. Single daily doses of MK-0991 should provide adequate systemic levels of fungicidal activity as a result of its long half-life pharmacokinetics, wide distribution, and slowly accumulating concentrations in tissue.     

Image-guided endoscopic surgery: results of accuracy and performance in a multicenter clinical study using an electromagnetic tracking system

Image-guided surgery has recently been described in the literature as a useful technology for improved functional endoscopic sinus surgery localization. Image-guided surgery yields accurate knowledge of the surgical field boundaries, allowing safer and more thorough sinus surgery. We have previously reviewed our initial experience with The InstaTrak System. This article presents a multicenter clinical study (n=55) that assesses the system's capability for localizing structures in critical surgical sites. The purpose of this paper is to present quantitative data on accuracy and performance. We describe several new advances including an automated registration technique that eliminates the redundant computed tomography scan, compensation for head movement, and the ability to use interchangeable instruments.     

浅谈地源热泵

概述了地源热泵系统的工作原理、组成、分类及特点,分析了影响地源热泵系统性能的因素,阐述了地源热泵在国内外的发展状况,指出了在国内发展地源热泵所面临的一些问题,展望了地源热泵的发展前景。     

Correlation between in vitro and in vivo parameters of commercial paracetamol tablets

Three leading and competitive commercial products of paracetamol tablets coded as brands A, B and C (A, being the innovator product) in the country were evaluated for their in vitro properties and in vivo comparative bioavailability. The studies included chemical equivalence, hardness, disintegration time, dissolution rate and systemic availability among eight healthy volunteers. The disintegration times were 2.1 min for brand A, 5.7 min for brand B and 36.2 min for brand C. The dissolution rate (T70) were 33.0 min, 74.5 min and 56.5 min for brands A, B and C, respectively. While brand A passed all the in vitro tests as specified in the official monograph, brand B failed only the dissolution rate test and brand C failed both the disintegration and dissolution tests. These significant differences observed among the products after in vitro tests were not reflected in the in vivo availability. While the absorption rate (indicated by tmax) of brand C was significantly faster (i.e. shorter) than those of Brands A and B, the extent of absorption (indicated by AUC) was comparable among the three brands. The relative bioavailabilities (with respect to brand A) were 92 and 91% for brands B and C, respectively indicating that the products were bioequivalent. Comparison of the in vitro and in vivo data suggest that the systemic absorption of paracetamol may not be dissolution--rate limited and that using in vitro dissolution rate studies alone to establish bioequivalency of paracetamol tablets should be done with caution.     

European research policy and bibliometric indicators, 1990�C2005

This paper describes and analyses the role played in the development of bibliometric indicators??and the use made of bibliometric indicators for policy purposes??by the European Commission??s Directorate-General Research in the period 1990?C2005.     

A randomized, controlled trial of a behavioral intervention to prevent sexually transmitted disease among minority women

Using annual bite-wing radiographs, the incidence and progression of approximal caries (4d-7m) were assessed longitudinally in teenagers and adolescents whose treatment had been based on remineralizing rather than restorative strategies. A closed cohort of 536 children initially was followed from 11 to 22 years of age. The scoring system was: 0 = no visible radiolucency; 1-2 = radiolucency in the enamel up to the enamel-dentin border; 3 = radiolucency with a broken enamel-dentin border but with no obvious progression in the dentin; 4 = radiolucency with obvious spread in the outer half of the dentin, and 5 = radiolucency in the inner half of the dentin. Caries rates were estimated as the number of new lesions/100 tooth surface-years, and the Kaplan-Meier estimate was used to calculate the cumulative survival time of each approximal surface. Three events were used: the transitions from states 0 to 2, 2 to 4 and 3 to 4. The results showed a considerable variation between the surfaces in both caries rates and survival time. For all surfaces combined, the median caries rate from state 0 to 2 was 3.9 new lesions/100 tooth surface-years; from state 2 to 4, the rate was 5.4, and from state 3 to 4 it was 20.3. Of the sound surfaces (state 0), 75% survived 6.3 years without reaching state 2. Given state 2, 75% survived 4.8 years without reaching the outer half of the dentin (state 4), while given a lesion at the enamel-dentin border (state 3), 75% survived 1.3 years without doing the same. The median survival time of lesions from state 3 to 4 was 3.1 years. The group with DMFSappr>1 at the age of 11-12 years had a risk of new approximal enamel lesions (state 0-2) that was 2.5 times greater than that of the group with DMFSappr = 0-1.