Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy

BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of "high beef consumers" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of "high beef consumers" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.     

基于物体空间序法的CT图像三维重建算法的研究

首先对三维可视化方法进行了分类概述。接着对基本的物体空间序法及其改进算法——抛雪球法做了详细的描述，并且通过对两组CT数据进行三维重建实验，得到高质量的重构图像。最后，本文研究并采用了提取表面体素进行体绘制加速的方法，实现了基于等值面提取表面的加速算法，实验证明加速算法能够满足显示要求并能起到明显的加速作用。     

A centralised, automated dental hospital water quality and biofilm management system using neutral Ecasol™ maintains dental unit waterline output at better than potable quality: A 2-year longitudinal study

Most studies addressing biofilm formation in dental chair unit waterlines (DUWLs) have focused on a range of individual dental chair units (DCUs) and no studies on a centralised approach in a large number of DCUs have been reported to date.

Objectives

To develop a centralised, automated water quality and biofilm management system serving the distribution network providing water to Dublin Dental Hospital's 103 DCUs, capable of maintaining DUWL supply and output water at better than potable quality standards in the long-term and requiring a minimum of human intervention. The potable water standard for the European Union does not specify an upper limit of aerobic heterotrophic bacteria, whereas a maximum of 100 cfu/mL is permitted in bottled water.

Methods

Mains water of varying quality was treated by specifically selected automated filtration units to provide DCUs with water of consistent chemical composition. This water was then automatically disinfected using an electrochemically activated solution Ecasol™ (Trustwater Group, Clonmel, Ireland) (2.5 ppm) prior to distribution to DCUs. Microbiological quality of both DUWL supply and output water was monitored weekly by culture on R2A agar for 10 sentinel DCUs for a 100-week period. DUWLs were tested for the presence of biofilm by electron microscopy.

Results

Chemical composition of processed mains water consistently bettered potable water standards. DUWL supply water and output water aerobic heterotrophic bacterial counts averaged <1 and 18.1 cfu/mL, respectively, from the 10 DCUs, compared to 88 cfu/mL for unprocessed mains water. This correlated with the absence of biofilm in DUWLs. No adverse effects due to Ecasol™ treatment of supply water were observed for DUWLs or DCU instruments.

Conclusions

This centralised and automated water treatment and biofilm management system consistently maintains DUWL output water at better than potable quality simultaneously in a large number of DCUs over the long-term.     

Effects of vasodilator therapy for severe pump failure in acute myocardial infarction on short-term and late prognosis.

Forty-three patients with severe pump failure complicating acute myocardial infarction were treated with vasodilators (nitroprusside (40) and phentolamine (3)) for four hours to 27 days. Cardiac index, stroke volume index, and stroke work index (SWI) increased while the left ventricular filling pressure (LVFP) decreased during vasodilator therapy. Twenty-four of the 43 patients (56%) survived. Of patients with initial SWI between 11-20 gm-m/m2 and LVFP less than 15 mm Hg, 68% survived. In contrast only 18% of patients with SWI of 10 gm-m/m2 or less and LVFP greater than 15 mm Hg survived. Of the 17 patients with clinical shock, 8 (47%) survived. All 24 patients discharged from the hospital were followed for at least 12 months. Fourteen patients died one to 25 months (average 9.2 months) after discharge and the cause of death was pump failure in ten of them (71%). The ten survivors at last follow-up had been followed for 15 to 32 months (average 24 months). The cumulative survival at 24 months was 28%. Thus, despite improvement in short-term prognosis with vasodilator therapy in patients with severe pump failure complicating acute myocardial infarction, the prognosis for long term survival remains unfavorable, possibly due to severe intrinsic cardiac damage.     

Myocardial salvage by intracoronary thrombolysis in evolving acute myocardial infarction: evaluation using intracoronary injection of thallium-201

Immediate objective assessment of viabillty of reperfused myocardium following intracoronary (IC) thrombolysis by evaluation of ventricular function may be limited due to delay in restoration of function. Thus we assessed myocardial uptake of thallium-201 (TI-201) following IC injection postreperfusion as an index of myocardial salvage in 12 experimental dogs and in five patients with evolving acute myocardial infarction (AMI). In seven dogs with mean of 313 minutes of experimental coronary occlusion, immediate postreperfusion IC TI-201 images revealed absence of myocardial uptake in prevlously occluded zones. These TI-201 defects correlated with presence of necrosis as demonstrated by histochemical staining with triphenyl-tetrazolium chloride (TTC). In contrast, in five dogs with mean of 37 minutes of coronary occlusion, reperfused myocardium showed normal TI-201 uptake following its IC injection; this normal TI-201 uptake pattern correlated with absence of necrosis by TTC technique in all five dogs. In five patients with evolving AMI, control TI-201 images obtained following IV injection prior to IC thrombolysis showed myocardial perfusion defects corresponding to distribution of the occluded vessel. Following reperfusion, 30 to 50 mCi of TI-201 was injected into the reopened coronary artery. In two patients with mean symptom onset of reperfusion time of $\text{2}\text{1}\text{2}\text{hours}$, immediate postreperfusion IC TI-201 images demonstrated normal or improved TI-201 uptake in reperfused myocardium. By radionuclide ventriculography, segmental wall motion remained abnormal in the reperfused regions 6 hours postreperfusion and showed improvement by the time of 10-day study. In the remaining three patients with symptom onset to reperfusion time of 5 hours, immediate postreperfusion IC TI-201 images did not show improvement, correlating with persistent wall motion abnormalities 10 days postreperfusion. In all five patients, repeat 10-day IV TI-201 images were unchanged from the immediate postreperfusion IC TI-201 images. We conclude that (1) prereperfusion TI-201 imaging with repeat TI-201 injection into the reopened coronary artery appears to delineate the extent of myocardial salvage in both experimental and clinical studies and (2) this method of IC TI-201 imaging allows immediate assessment of myocardial viabillty which may facilltate decisions regarding the need for additional myocardial revascularization modalities.     

The effect of acute and repeated ischemic preconditioning on recovery following exercise-induced muscle damage

ObjectivesThe aim of this investigation was to determine if acute or repeated applications of ischemic preconditioning (IPC) could enhance the recovery process, following exercise induced muscle damage (EIMD).DesignRandomized control trial.MethodsTwenty-three healthy males were familiarised with the muscle damaging protocol (five sets of 20 drop jumps from a 0.6 m box) and randomly allocated to one of three groups: SHAM (3 × 5 min at 20 mmHg), Acute IPC (3 × 5 min at 220 mmHg) and Repeated IPC (3 days x 3 × 5 min at 220 mmHg). The indices of muscle damage measured included creatine kinase concentration ([CK]), thigh swelling, delayed onset muscle soreness, counter movement jumps (CMJ) and maximal voluntary isometric contraction (MVIC).ResultsBoth acute and repeated IPC improved recovery in MVIC versus SHAM. Repeated IPC led to a faster MVIC recovery at 48 h (101.5%) relative to acute IPC (92.6%) and SHAM (84.4%) (P < 0.05). Less swelling was found for both acute and repeated IPC vs. SHAM (P < 0.05) but no group effects were found for CMJ, soreness or [CK] responses (P > 0.05).ConclusionTaken together, repeated IPC can enhance recovery time of MVIC more than an acute application, and both reduce swelling following EIMD, relative to a SHAM condition.     

Potent in vitro and in vivo antitoxoplasma activity of the lipid-soluble antifolate trimetrexate.

Trimetrexate, a highly lipid-soluble quinazoline antifolate now undergoing trials as an anticancer agent, was found to be a potent inhibitor of the dihydrofolate reductase (DHFR) isolated from Toxoplasma gondii. The concentration required for 50% inhibition of protozoal DHFR was 1.4 nM. As an inhibitor of this enzyme, trimetrexate was almost 600-fold (amount of antifolate required to inhibit catalytic reaction by 50%) and 750-fold (inhibition constant) more potent than pyrimethamine, the DHFR inhibitor currently used to treat toxoplasma infection. When the protozoan was incubated with 1 microM trimetrexate, the drug rapidly reached high intracellular concentrations. Since toxoplasma organisms lack a transmembrane transport system for physiologic folates, host toxicity can be prevented by co-administration of the reduced folate, leucovorin, without reversing the antiprotozoal effect. The effectiveness of trimetrexate against toxoplasma was demonstrated both in vitro and vivo. Proliferation of toxoplasma in murine macrophages in vitro was completely inhibited by exposure of these cells to 10(-7) M trimetrexate for 18 h. When used alone, trimetrexate was able to extend the survival of T. gondii-infected mice.