人脑胶质瘤中P53和VEGF 的表达及意义

目的 探讨胶质瘤组织中血管内皮生长因子(VEGF)和P53蛋白的表达及其临床意义。方法 应用免疫组织化学技术对50例胶质瘤组织进行P53、VEGF表达的检测。结果 P53、VEGF的表达均随胶质瘤病理级别的升高而升高。Ⅰ～Ⅳ级病理分级中P53阳性率分别为22．22％(4／18)，65％(13／20)，75％(9／12)；VEGF阳性率分别为27．78％(5／18)，90％(18／20)，100％(12／12)。P53、VEGF的表达均与胶质瘤病理分级显著相关(P＜0．01)，P53和VEGF阳性表达符合率为76％(38／50)，两者的表达有显著性相关(P＜0．01)。结论 P53和VEGF蛋白的表达是判断胶质瘤生物学行为的重要指标；胶质瘤组织突变的P53基因可上调VEGF的表达，促进血管生成，进而影响胶质瘤的进展。     

新生儿病房铜绿假单胞菌的血清学分型,质粒分析研究

新生儿病房１９８９年１０月～１９９０年１２月、１９９６年３～６月两个时间段分离４０株铜绿假单胞菌，血清学分型率９７．５％，第一时间段以Ｏ１１型最多，占３０．４％，集中在１９９０年６～１０月，第二时间段Ｏ３型占９３．８％，集中在１９９６年３～６月，表明该病房发生两次铜绿假单胞菌医院感染流行。质粒检出率４２．９％，Ｏ１１型菌株质粒谱为８．１、４６．５、１７９．１ｋｂ，并经ＨｉｎｄⅢ酶切进一步证实为同一克隆。对氟哌酸、阿米卡星及头孢他啶的敏感率分别为１００％、９７．３％和９５％。对庆大霉素耐药率明显上升，提示控制铜绿假单胞菌医院感染的重要性。     

Smooth muscle of rabbit isolated aorta contains the NK-2 tachykinin receptor

Summary Neurokinin A, neurokinin B and substance P caused concentration-related contractions of rabbit isolated aorta with pD₂ values of 8.1, 6.9 and 6.0, respectively. [D-Pro², D-Trp^7,9]-substance P, a competitive tachykinin antagonist, had pA₂ values of 5.3 against neurokinin A, 5.1 against neurokinin B and 5.2 against substance P indicating that tachykinin receptors mediated responses to the agonists. [pGIu⁵,MePhe⁸,-McGly⁹]-substance P 5–11 (DiMe-C7), senktide and septide did not contract the aorta. It is concluded that of the known tachykinin receptors smooth muscle of the rabbit isolated aorta contains only the NK-2 type. Send offprint requests to J. W. Constantine at the above address     

P_(27)、PCNA与IgA肾病中医证型及病理类型的关系

目的 :运用免疫组化方法研究原发性IgA肾病患者肾组织中细胞周期调控蛋白P2 7(P2 7)、增殖细胞核抗原PCNA(PCNA)的表达 ,探讨两者与IgA肾病病理分级及其与中医证型之间的关系。 方法 :选择行肾穿刺活检的IgA肾病住院患者 5 2例 ,并按照中医辨证分型标准将其分为肺肾气虚证、脾肾阳虚证、肝肾阴虚证、气阴两虚证、血瘀证、湿热证六型。系膜增生的病理组织学分为 4级。运用免疫组化方法检测P2 7、PCNA的表达。结果 :(1)IgA肾病各个病理分级P2 7、PCNA的表达两两比较有统计学意义。显示随着系膜细胞增生的病理分级程度增高 ,PCNA的表达增高 ,而P2 7的表达则按相反方向进行。病理分级和P2 7、PCNA表达的等级相关性检验 (Spearman法 )显示 :P2 7的表达与病理类型呈非常显著负相关 ,而PCNA的表达与病理类型呈显著正相关。 (2 )IgA肾病三个中医证型的病理分级之间有统计学意义 ,其中气阴两虚证的病理分级比湿热证、肝肾阴虚证高 ,湿热证与肝肾阴虚证的病理分级之间无统计学意义。 (3)随着湿热→肝肾阴虚→气阴两虚的进展 ,P2 7的表达呈现出逐渐减少的趋势 ,而PCNA的表达呈现出逐渐增加的趋势。结论 :(1)P2 7、PCNA作为判断IgA肾病肾脏组织学损伤程度和预后的指标值得深入研究。 (2 )IgA肾病中医证型之间病理分     

Effects of adenosine 5’-triphosphate, uridine 5’-triphosphate, adenosine 5’-tetraphosphate and diadenosine polyphosphates in guinea-pig taenia caeci and rat colon muscularis mucosae

The functional effects of adenosine 5’-triphosphate (ATP), uridine 5’-triphosphate (UTP), adenosine 5’-tetraphosphate (AP₄) and the diadenosine polyphosphates P₁,P₃-diadenosine triphosphate (Ap₃A), P₁,P₄-diadenosine tetraphosphate (Ap₄A) and P₁,P₅-diadenosine pentaphosphate (Ap₅A) were studied in two isolated smooth muscle preparations thought to contain P_2Y (P2Y₁) receptors, the guinea-pig taenia caeci (which relaxes to ATP) and the rat colon muscularis mucosae (which contracts to ATP). In addition, the breakdown of these compounds by the rat colon muscularis mucosae was investigated by high pressure liquid chromatography. In the guinea-pig taenia caeci all the purine nucleotides caused relaxation with a potency order of Ap₃A=Ap₄A> ATP>AP₄=Ap₅A, and these relaxations were antagonised by suramin with apparent pA₂ values in the region of 5, consistent with activation of a P2Y₁ receptor. In the rat colon muscularis mucosae the nucleotides caused contraction with a potency order of Ap₃A = Ap₄A>ATP=AP₄ =Ap₅A >UTP. However, while suramin (100 μM) inhibited responses to ATP and UTP at all concentrations of agonist, it only inhibited contractions induced by the higher concentrations of AP₄, Ap₃A and Ap₄A and had little effect on contractions induced by Ap₅A. A higher concentration of suramin (1 mM) enhanced contractions induced by ATP but greatly inhibited those induced by UTP and had no effect on responses to the other agonists. The A₁ adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM) had no effect on responses to ATP or UTP but inhibited responses to Ap₃A, Ap₄A, Ap₅A and AP₄. A combination of suramin (1 mM) and DPCPX (10 nM) almost abolished responses to all the agonists. ATP and UTP were rapidly degraded by the rat colon muscularis mucosae while AP₄, Ap₃A, Ap₄A and Ap₅A were degraded more slowly, and the major product detected after breakdown of the purine nucleotides was inosine rather than adenosine. The breakdown of all the nucleotides was inhibited by suramin (1 mM), although this inhibition did not achieve statistical significance in the case of ATP. These results show that while the diadenosine polyphosphates appear to act as P2 agonists in the taenia caeci, in the rat colon muscularis mucosae their major action is via adenosine A₁ receptors rather than via P2 receptors. In addition, although they are more stable than ATP or UTP, their action in this tissue is clearly affected by their degradation which complicates the effects of suramin. Received: 23 March 1998 / Accepted: 29 June 1998     

Plasma kinetics of 125I-labelled amyloid P component in {beta}2M amyloidosis: A possible approach to quantitate disease activity

Dialysis amyloidosis is one of the most incapacitating complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered P>125P>I-labelled serum amyloid P component(P>125P>I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. P>125P>I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of P>125P>I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma P>125P>I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis.     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Immunoregulatory Effect of Substance P in Human Eosinophil Migratory Function

Substance P (SP) is a tachykinin involved in the regulation of inflammatory processes. To investigate a modulatory role of the neuropeptide SP in allergic inflammation, we studied its priming effect on human eosinophil chemotaxis and kinetic responses towards platelet activating factor (PAF) and recombinant human interleukin 5 (rhlL-5). Blood was obtained from normal subjects and eosinophils were separated by Percoll discontinuous density gradient centrifugation. High purification was obtained by negative selection procedure (CD16-beads) and the experiments were performed in a 48-well microchemotaxis Boyden chamber. In the present study we demonstrate a potent synergistic effect of 100nM dose of SP on the migratory function of human eosinophils stimulated by PAF and rhIL-5. This synergism was chemotaxis specific and was abolished by NK-1 receptor antagonist (FK888). The results suggest that neurogenic stimuli may play a significant role in eosinophil infiltration via its priming effect on the cell.     

In vivo 31P NMR studies of paraplegics' muscles activated by functional electrical stimulation

The bioenergetics of paralyzed muscles of spastic paraplegic patients under functional electrical stimulation (FES) was studied in vivo using ³¹P NMR. The protocol included rest, 3 min of induced tetanic isometric contraction through surface electrodes and 40 min of recovery. The continuous stimulation, the force recording and the ³¹P NMR measurements were sampled simultaneously inside the whole body imager. Normal values were found for the phosphorous metabolite ratios at rest. During contraction, prominent changes were detected including: a) accumulation of inorganic phosphate (P) accompanied by an unusually strong signal in the phosphomonoester (PME) region, b) phosphocreatine (PCr) decline, and c) a decrease in the intracellular pH. In the following recovery period the physiological state of the muscle was monitored and quantitated by ³¹P NMR. No metabolic and mechanical irreversible damage was detected in the paraplegics' muscles activated by FES under our experimental conditions.