MAPK反义寡核苷酸诱导大鼠成纤维细胞凋亡的研究

目的 探讨MAPK反义寡核苷酸（antisense oligodeoxynucleotide，ASO）对大鼠肾成纤维细胞凋亡的影响。方法 脂质体转染法将MAPK反义寡核苷酸导入NRK-49F细胞中，Western—blotting测定细胞内MAPK蛋白的表达。DAPI染色观察细胞形态，流式细胞术检测细胞凋亡比率。结果 MAPKASO降低细胞MAPK蛋白含量；且可促进细胞凋亡，转染细胞出现凋亡特征性改变，凋亡率为35．8％，与其余各组有显著差异（P〈0．05）。结论 MAPK反义寡核苷酸通过阻断信号转导分子MAPK诱导大鼠成纤维细胞细胞凋亡，为防治肾移植术后间质纤维化提供一定的理论依据。     

Sequence, genetics and serology of a new HLA-B allele: B*4903

A new HLA-B allele - B*4903 - was detected by the polymerase chain reaction using sequence-specific priming (PCR-SSP), in a Caucasoid bone marrow panel donor, that differs from B*4901 by 8 nucleotides at positions 141, 142, 144, 165, 167, 193, 206 and 213 in exon 2. These substitutions all occur in HLA-B*51 and B*52 alleles and encode 4 amino acid substitutions at positions 24 (Thr to Ala), 32 (Leu to Gln), 41 (Thr to Ala) and 45 (Lys to Thr). This suggests that B*4903 occurred following a gene conversion-like event involving B*4901 and probably a B*51 allele. HLA-B*4903 was identified on a haplotype with: HLA-A*0201; Cw*07; DRB1*1302/34; DRB3*0301; DQA1*0102; DQB1*0604; BfS; C4A3; C4BQ0 and encodes a unique serological specificity which was characterised by the reactivity of 55 antisera directed towards at least four predicted epitopes. No further examples of B*4903 were found in 15,796 consecutive HLA PCR-SSP typed donors from the Welsh Bone Marrow Donor Registry, indicating that this allele has a phenotype frequency of <0.01% and a gene frequency of <0.00004.     

Overshoot in <Emphasis Type="Italic">V̇</Emphasis>O<Subscript>2</Subscript> following the onset of moderate-intensity cycle exercise in trained cyclists

We have previously observed that following the onset of moderate intensity cycle ergometry, the pulmonary O₂ uptake (O₂) in trained cyclists often does not increase towards its steady-state value with the typical mono-exponential characteristics; rather, there is a transient overshoot. The purpose of this study was to systematically examine this phenomenon by comparing the O₂responses to two moderate-intensity work rates and one high-intensity work rate in trained and untrained subjects. Following a ramp exercise test to the limit of tolerance for the determination of the gas exchange threshold (GET) and O_2peak, seven trained cyclists [mean (SD); O_2peak 66.6 (2.5) ml·kg^–1·min^–1] and eight sedentary subjects [O_2peak 42.9 (5.1) ml·kg^–1·min^–1] completed six step transitions from baseline cycling to work rates requiring 60% and 80% GET and three step transitions from baseline cycling to a work rate requiring 50% of the difference between GET and O_2peak (50%). O₂ was measured breath-by-breath and modelled using standard techniques. The sedentary subjects did not overshoot the steady-state O₂ at any intensity. At 60% GET, six of the seven cyclists overshot the steady-state O₂ [by an integral volume of 164 (44) ml between ~45 and 125 s]. At 80% GET, four of the seven cyclists overshot the steady-state O₂ [by an integral volume of 185 (92) ml between ~55 and 140 s]. None of the cyclists showed an overshoot at 50%. These results indicate that trained cyclists evidence an overshoot in O₂ before steady-state is reached in the transition to moderate-intensity exercise. The mechanism(s) responsible for this effect remains to be elucidated, as does whether the overshoot confers any functional or performance benefit to the trained cyclist.     

Combined trisomy 1q and monosomy 7q due to translocation 1;7 in myelodysplastic syndromes

Two patients, possibly exposed to toxic agents, presented with a myelodysplastic syndrome (MDS) and a t(1;7) in bone marrow metaphases. This observation confirms the occurrence of this characteristic chromosome anomaly in MDS and its possible induction by environmental agents. It is hypothesized that this t(1;7) MDS may not be confined to a particular geographical area but that, in the past, it may have been overlooked in the absence of optimal banding, which is obviously necessary to identify the anomaly.     

Inflammatory effects of snake venom myotoxic phospholipases A2

Snake venom phospholipases A₂ (PLA₂) show a remarkable functional diversity. Among their toxic activities, some display the ability to cause rapid necrosis of skeletal muscle fibers, thus being myotoxic PLA₂s. Besides myotoxicity, these enzymes evoke conspicuous inflammatory and nociceptive events in experimental models. Local inflammation and pain are important characteristics of snakebite envenomations inflicted by viperid and crotalid species, whose venoms are rich sources of myotoxic PLA₂s. Since the discovery that mammalian PLA₂ is a key enzyme in the release of arachidonic acid, the substrate for the synthesis of several lipid inflammatory mediators, much interest has been focused on this enzyme in the context of inflammation. The mechanisms involved in the proinflammatory action of secretory PLA₂s are being actively investigated, and part of the knowledge on secretory PLA₂ effects has been gained by using snake venom PLA₂s as tools, due to their high structural homology with human secretory PLA₂s. The inflammatory events evoked by PLA₂s are primarily associated with enzymatic activity and to the release of arachidonic acid metabolites. However, catalytically inactive Lys49 PLA₂s trigger inflammatory and nociceptive responses comparable to those of their catalytically active counterparts, thereby evidencing that these proteins promote inflammation and pain by mechanisms not related to phospholipid hydrolysis nor to mobilization of arachidonic acid. These studies have provided a boost to the research in this field and various approaches have been used to identify the amino acid residues and the specific sites of interaction of myotoxic PLA₂s with cell membranes potentially involved in the PLA₂-induced inflammatory and nociceptive effects. This work reviews the proinflammatory and nociceptive effects evoked by myotoxic PLA₂s and their mechanisms of action.