Regeneration of kidney tubular epithelial cells

Conclusion The mechanisms that regulate regeneration of kidney epithelial cells after acute tubular necrosis are poorly understood. Repair of the nephron can take place in the adverse systemic metabolic setting caused by failure of renal function. This clinical observation suggests that factors released at the site of the tubular insult can mediate repair. Studies carried out in this and other laboratories show that kidney epithelial cells can release and respond to polypeptide growth factors which may thereby contribute to renal regeneration by autocrine and paracrine mechanisms. Specific growth factors secreted by cells and deposited in the tubular basement membrane prior to injury may subsequently participate in nephron repair. In addition, adenine nucleotides released from injured or dying cells at the injury site or provided exogenously could stimulate surviving renal epithelial cells at the edges of the wound to migrate along the basement membrane to rapidly reepithelialize the nephron and subsequently initiate mitogenesis to replace cells lost by necrosis.The nephrotoxic effect of many agents used in cancer chemotherapy and the older age of patients undergoing complicated surgical procedures has increased the incidence of ARF, whereas the mortality rate has not changed since the early 1950s [22]. Thus there is considerable need for innovative therapeutic strategies. An important goal of future research efforts is to identify new growth factors that facilitate migration, differentiation, and proliferation of renal epithelial cells at sites of tubular necrosis. Isolation and use of these agents in combination with dialysis and nutritional support could speed renal regeneration and thereby improve the outcome in patients with this condition.Abbreviations ARF acute renal failure - ECM extracellular matrix - EGF epidermal growth factor - FGF fibroblast growth factor - IGF insulin-like growth factor - MGSA melanocyte growth-stimulating activity - PDGF platelet-derived growth factor - IGF transforming growth factor     

胸导管引流对慢性哮喘病人外周血淋巴细胞内环核苷酸代谢的影响

观察7例慢性哮喘病人胸导管引流治疗前后外周血淋巴细胞内 cAMp/cGMP 值的变化。结果发现,慢性哮喘病人外周血淋巴细胞内 cAMP/cGMP 的值较正常人低(P<0.001);胸导管引流治疗后,哮喘病人外周血淋巴细胞内 cAMP/cGMP 值较治疗前升高(P<0.01)。提示,慢性哮喘病人外周血淋巴细胞功能异常、活性增强,这可能是哮喘发病的重要原因之一。胸导管引流引起的免疫抑制作用,一个重要的机理就是影响淋巴细胞内环核苷酸的代谢,而使淋巴细胞的活性降低,这可能也是胸导管引流治疗慢性哮喘的机理之一。     

Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites

The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75  mg/m² MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children ( n =21) who tolerated 100% dosages and who were matched in this respect with a similar group of UKALL X children. Red blood cell MP derived thioguanine nucleotide (TGN) concentrations were measured in both groups under comparable conditions; at 75  mg/m² MP there was no significant difference. MP dose escalation in the UKALL XI children produced higher TGN concentrations (TGNs at 100% vs 125% dosages, median difference 90  pmol/8×10⁸ RBCs, 95% CI 25 to 165  pmol, P <0.02). Assayed at the time of cytopenia induced dose reduction, the UKALL XI children had accumulated significantly higher TGN concentrations than the UKALL X children (median difference 78  pmol/8×10⁸ RBCs, 95% CI 20 to 144, P <0.02). These findings indicate that dose escalation in children tolerant of 100% MP dosages produces higher peak TGN concentrations.     

自动平衡记录仪与HPLC匹配定量测定腺苷酸

本文以腺苷酸为测定物,探讨了以国产自动平衡记录仪为高效液相色谱记录并定量分析结果的方法。结果表明,从自动平衡记录上得到峰形、计算结果均与原机所带积分仪的一致。其稳定性、灵敏度和线性响应均能达到高效液相色谱检测器的要求,是一种可以代替积分仪分析结果的经济、可靠的方法。     

18氟-胸腺嘧啶核苷正电子发射体层-CT显像在胸部肿瘤上的初步研究

目的：评价^18氟-胸腺嘧啶核苷（^18F-FLT）正电子发射体层（PET）-CT显像对胸部肿瘤定性诊断的价值。方法：对17例做了^18氟-脱氧葡萄糖（^18F-FDG）PET-CT检查，但定性诊断困难的患者，在第2～3天进行了^18F-FLITPET-CT显像。分析病变在两种不同显像剂PET-CT上的表现，分别测量二者的最大标准摄取值（maxSUV）。结果：8例恶性病变（5例肺癌、1例纵隔淋巴瘤、1例胸椎恶性肿瘤、1例胸椎转移瘤），其中7例见FLT异常摄取，5例肺癌平均maxSUV为4．2（鳞癌2例、腺癌2例、肺泡癌1例）；9例良性病变（5例肺结核、1例肺炎、3例纵隔淋巴结结核）无或轻度摄取FLT，其中6例肺内良性病变平均maxSUV为1．6；9例良性病变中8例见FDG异常浓聚，其中6例肺内良性病灶平均maxSUV为3．9，3例纵隔淋巴结结核也见FDG明显摄取，平均maxSUV为11．0。11例肺内病灶FDG和FLT显像的敏感性、特异性、准确性分别为100．0％（5／5）、16．7％（1／6）、54．5％（6／11）和80．0％（4／5）、66．7％（4／6）、72．7％（8／11）。结论：胸部肿瘤^18F-FLT显像的特异性较高，在^18F-FDG显像阳性，难以确定病变性质时，FLIT可以作为FDG的有益补充，二者联合显像有助于提高胸部肿瘤诊断的准确性。     

Two novel gastric cancer-associated genes identified by differential display

AIM To clone novel gastric cancer-associated genes and investigate their roles in gastric cancer occurrence.METHODS A method called differential display was used which allows the identification of differentially expressed genes by using PAGE to display PCR-amplified cDNA fragments between gastric cancer cells and normal gastric mucosa cells. These fragments were cloned into plasmid vector pUC18. Homology analysis was made after sequencing these fragments.RESULTS Two novel genes were identified compared with sequences from GenBank. One was registered with the AD number AF 051783. In situ hybridization showed that these two novel genes expressed specifically in gastric cancer tissues.CONCLUSION The two novel genes obtained by differential display were confirmed to be gastric cancer-associated genes using in situ hybridization.     

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of α-latrotoxin (αLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N^ω-nitro-L-arginine (L-NOARG: 0.3 mM) both αLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions αLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 μM ω-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or ω-conotoxin GVIA, the αLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and ω-conotoxin GVIA further reduced or abolished the relaxation. In preparationstreated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, αLTX and EFS had no effects. αLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and ω-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. αLTX caused a major loss of both types of vesicle. The present data suggest that αLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra. Received: 13 January 1997 / Accepted: 17 April 1997     

Abnormal nucleotide pattern in the eosinophils of a patient with acute lymphoblastic leukemia associated with eosinophilia

In this article we present a patient with acute lymphoblastic leukemia (ALL) associated with eosinophilia, in which the eosinophilia preceded a meningeal and bone-marrow relapse of ALL. We analysed the purine and pyrimidine nucleotide content of the eosinophils (92% pure) and compared the nucleotide pattern with that of eosinophils from healthy donors and from patients with eosinophilia not associated with leukemia. The ratios of purine : pyrimidine and of uracil :cytosine nucleotides were decreased compared with those in eosinophils from healthy donors and from patients with eosinophilia with other aetiologies. The total nucleotide concentration was increased, especially the concentration of UDP-sugars and pyrimidine nucleotides.

The decrease in these ratios and the increase in concentration of the nucleotides and the UDPsugars were also detected in leukemic cells of patients with ALL (de Korte et al., Leukemia Res. 10, 389–396 (1986)) compared to normal lymphocytes. We suggest a malignant character of the eosinophils in our patient with ALL associated with eosinophilia, in contrast with the nonmalignant state suggested previously for these cells.     

Can adenine nucleotides predict primary nonfunction of the human liver homograft?

Sixty-eight primary liver grafts were analyzed to see whether adenine nucleotides (AN: ATP, ADP, and AMP) or purine catabolites (PC: adenosine, inosine, hypoxanthine, and xanthine) of tissue or effluent can predict primary graft nonfunction. AN, PC, and nicotinamide adenine dinucleotide, oxidized form (NAD⁺) of the tissue before (pretransplant) and after graft reperfusion (post-transplant) and of the effluent were analyzed. The graft outcome was classified into two groups (group A: successful, n=64; group B: primary nonfunctioning, n=4). No significant differences were observed in pretransplant measurements between groups A and B, whereas ATP, ADP, total AN, total AN+total PC (T) and NAD⁺, in post-transplant tissues, were significantly higher in group A. Xanthine in the effluent was significantly higher in group B than in group A. ATP, ADP, total AN, T, and NAD⁺ in post-transplant tissue were significantly associated with primary graft nonfunction by logistic regression analysis.