The nature of polymorphism of the HLA-DRB intron sequences is lineage specific

Abstract: The sequence database of HLA-DRB genes is mainly derived from mRNA analysis or has focused exclusively on the polymorphism of the 2nd exon. Little is known about the non-coding sequences of the different DRB alleles which represent about 94% of the genes. In this study we have determined the sequence of the 3' 500 bp intron 1 fragment adjacent to exon 2 in all serologically defined HLA-DRB genes and their most frequent allelic subtypes. The intron sequences turned out to be highly polymorphic. Similar to the class I introns, this variability was not characterized by random point mutations but by a highly systematic diversity reflecting the lineage-specific relationship of the HLA-DR alleles. With a few exceptions in DRB1*15, 13 and 08 as well as DRB 4 and 5, the variability mirrors the serological diversity. As well as delivering insight into the genetic relationship between the different DRB alleles, these sequences will provide an extremely valuable basis for developing advanced DRB sequencing strategies for clinical purposes.     

Morphological and biochemical correlates of chemical induced injury in the lung

We have reviewed some of the factors which contribute to lung damage by various toxicants. These include disposition of the chemical, its metabolism, individual cell type susceptibility and the potential for the tissue to repair. We have discussed the use of biochemical parameters to measure the functional activity of individual cell types in order to predict the damage to specific cell types and concluded that careful morphological analysis of lung tissue is likely to provide a more sensitive and informative measure of specific cell type injury. However, in order to investigate the mechanism of toxicity of pulmonary toxicants it is essential to establish the primary biochemical event that leads to cell damage and morphological change. The importance of separating the relevant biochemical change(s) from the cascade of biochemical events associated with dead and dying cells and the reparative response of the lung is emphasised.This report results from a discussion sponsored and organised by the Advisory Subgroup in Toxicology (AST) of the European Science Foundation's Standing Committee for the European Medical Research Councils and held at the Medical Research Council Toxicology Unit, Carshalton, U. K. Those taking part were: W. N. Aldridge (AST; as above); J. Bignon (Unit for Research in Renal and Pulmonary Pathology, University of Paris, Creteil, France); P. H. Burri (Section of Developmental Biology, Institute of Anatomy, University of Berne, Switzerland); G. M. Cohen (as above); D. Dinsdale (MRC Toxicology Unit, Carshalton U. K.); P. Hedqvist (Dept. of Physiology, Karolinska Institute, Stockholm, Sweden); D. Henschler (AST; Dept. of Toxicology and Pharmacology, University of Wurzburg, FDR); G. J. Laurent (Biochemistry Unit, Cardiothoracic Institute, University of London, London, U. K.); R. Lauwerys (AST Industrial and Medical Toxicology Unit, University of Louvain, Brussels, Belgium); F. Lembeck (AST; Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); N. Lery (AST; Poison Control Centre, Lyon, France); P. Moldeus (Dept. of Forensic Medicine, Karolinska Institute, Stockholm, Sweden); B. Nemery (MRC Toxicology Unit, Carshalton, U. K.); A. Saria (Dept. for Experimental and Clinical Pharmacology, University of Graz, Austria); L. L. Smith (as above);B. Terracini (AST; Dept. of Pathology and Cancer Epidemiology, University of Turin, Italy)     

Role of the pelvic floor in bladder neck opening and closure I: Muscle forces

The aim of the study was to identify the striated muscle forces hypothesized to assist bladder neck opening and closure in females. Cadaveric dissection was used to identify the levator plate (LP), the anterior portion of pubococcygeus muscle (PCM), the longitudinal muscle of the anus (LMA), and their relation to the bladder, vagina and rectum. X-ray video recordings were made during coughing, straining, squeezing and micturition in a group of 20 incontinent patients and 4 controls, along with surface EMG, urethral pressure and digital palpation studies. During effort, urethral closure appeared to be activated by a forward muscle force corresponding to PCM, and bladder neck closure by backward muscle forces corresponding to LP and LMA. During micturition the PCM force appeared to relax, allowing LP and LMA to pull open the outflow tract. The data appear to support the hypothesis of specific directional muscle forces stretching the vagina to assist bladder neck opening and closure.     

Can a Single Muscle Fiber Model the Features of Myocardial Stunning?

The exact mechanisms that cause myocardial stunning are still unclear. We previously utilized a computer model of the ventricle that was effective in modeling the dominant observable features of stunning, but it was not simple to implement. This led to the design of a single muscle fiber model. The mathematical model of a muscle fiber consisted of three elements: a contractile element, a series elastic element, and a parallel elastic element. The model created length waveforms based on time-dependent force and contractile stiffness functions. This model was initially evaluated by entering the same regional parameter values used in the global dual region ventricular model. First a reduction of the contractile stiffness function was applied by reducing the peak stiffness by 30%, and then the rates of activation and deactivation were reduced by 20% while maintaining the peak values constant. The three-element model produced results very similar to the canine and ventricular model. Thus, it is concluded that the simpler three-element model provides an accurate model of the myocardial tissue and its deficiencies during stunning.     

Effects of a Broad-spectrum Behavioral Medicine Treatment Program on Children with Refractory Epileptic Seizures: An 8-Year Follow-Up

We present an 8 year follow-up on a group of children with refractory epileptic seizures who participated in the early 1980s in a controlled group study on the effects of a broad-spectrum behavior modification treatment program on children with refractory epileptic seizures. In the original study, 18 children were divided into three groups: behavior modification group, attention control group, and control group. The purpose was to investigate the effects of a learning-based treatment program superimposed on a regular medical treatment program. Also, the effects of professional attention were evaluated. At the 10 week and 1 year follow-ups, only the group receiving the behavior modification intervention had a significantly reduced rate of seizure index. The present study investigates these same children 8 years later using the same methods of investigation for an additional 10 week period. The results indicate that a significant reduction in seizures was obtained only for the behavior modification group at the 8 year follow-up.     

The effects of a reduced exercise duration taper programme on performance and muscle enzymes of endurance cyclists

Summary The influence of tapering on the metabolic and performance parameters in endurance cyclists was investigated. Cyclists (n = 25) trained 5 days · week^–1, 60 min·day^–1, at 75–85% maximal oxygen consumption (VO_2max) for 8 weeks and were then randomly assigned to a taper group: 4D (4 days;n = 7), 8D (8 days;n = 6), CON (control, 4 days rest;n = 6), NOTAPER (non-taper, continued training;n = 6). Muscle biopsy specimens taken before and after training and tapering were analysed for carnitine palmityltransferase (CPT), citrate synthase, ß-hydroxyacyl CoA dehydrogenase (HOAD), cytochrome oxidase (CYTOX), lactate dehydrogenase, glycogen and protein. Significant increases inVO_2max (6%), a 60-min endurance cycle test (34.5%), oxidative enzymes (77–178%), glycogen (35%) and protein (34%) occurred following training. After the taper, HOAD and CPT decreased 25 % (P<0.05) and 26% respectively, in the CON. Post-taper CYTOX values were different (P<0.05) for 4D and 8D compared with CON. Muscle glycogen levels were increased (P<0.05) after tapering in the 4D, 8D and CON, but decreased in NOTAPER. Similarly, power output at ventilation threshold was significantly increased in the 4D (27.4 W) and 8D (27 W) groups, but decreased (22 W) in the NOTAPER. These findings suggest that tapering elicited a physiological adaptation by altering oxidative enzymes and muscle glycogen levels. Such an adaptation may influence endurance cycling during a laboratory performance test.     

曲肘式机构的优化设计

以功效系数为目标函数,相应地确定了设计变量和约束函数,对塑料注塑机合模机构的参数进行优化计算,提高了机构的综合性能。     

增生性玻璃体视网膜病变基质金属蛋白酶的定量研究

目的:研究增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)玻璃体中基质金属蛋白酶(matrix metalloproteinases,MMPs)的表达,探讨MMPs在PVR病理过程中的作用。方法:PVR患者采用标准三切口巩膜扁平部玻璃体切割术(pars plana vitrectomy,PPV),取未稀释的玻璃体21只眼,PPV术后复发的玻璃体腔液20只眼,意外死亡的正常人玻璃体10只眼,采用明胶酶谱分析法定量分析MMP-2和MMP-9活性水平。结果:PVR玻璃体有MMP-2活性水平增高,与正常玻璃体比较差异有显著性意义(P<0.05)。21眼PVR玻璃体中13只眼有MMP-9活性水平增高,平均(171.52±13.17)扫描单位。20眼PPV术后PVR复发的玻璃体腔液19只眼有MMP-9活性水平增高,平均(156.01±37.21)扫描单位。正常人玻璃体无MMP-9的表达。结论:PVR玻璃体有MMP-2和MMP-9活性水平增高,MMP-9活性水平增高可能与术后PVR复发有关。眼科学报2003;19:130-132。