The mycotoxin ochratoxin A is a substrate for phenylalanine hydroxylase in isolated rat hepatocytes and in vivo

Ochratoxin A (OTA), is a mycotoxin contaminating food and feed stuffs, consisting of a chlorinated dihydroisocoumarin linked through a 7-carboxyl group tol-phenylalanine by an amide bond. When OTA (0.12–1.4 mM) is incubated with freshly isolated rat hepatocytes, it inhibits both the hydroxylation of phenylalanine (0.05 mM) to tyrosine, catalyzed by phenylalanine hydroxylase and the subsequent metabolism of tyrosine as measured by homogentisate oxidation. The IC₅₀ of OTA for phenylalanine hydroxylation is 0.43 mM. OT, (0.5–1.0 mM), the dihydroisocoumarin moiety of OTA, does not inhibit phenylalanine hydroxylase activity under these conditions. During incubations of hepatocytes with uniformly labelled [³H]-OTA and unlabelled phenylalanine, tyrosine-ochratoxin A is formed (up to 6% of the total mycotoxin added), indicating that ochratoxin can act as a substrate for phenylalanine hydroxylase. In vivo tyrosine-OTA is also found in liver of poisoned animals.     

CD44v6蛋白在宫颈癌中的表达及其与预后因素的关系

目的 :了解CD44v6在宫颈上皮不典型增生、宫颈原位癌、宫颈浸润鳞癌及腺癌中的表达及其与预后因素的关系。方法 :用免疫组化法检测 10例正常宫颈上皮、15例宫颈上皮不典型增生、16例宫颈原位鳞癌、1例宫颈原位腺癌、2 7例宫颈浸润鳞癌、15例宫颈浸润腺癌中CD44v6蛋白的表达 ,实验结果以图像处理与分析系统进行半定量处理后进行统计分析。结果 :(1)着色部位主要为细胞膜 ,细胞浆不着色或着色较浅。细胞核被苏木素复染成淡蓝色。 (2 )CD44v6阳性表达正常宫颈上皮为 1/ 10 ,宫颈不典型增生为 7/ 15 ;宫颈鳞癌中原位癌为 7/ 16 ,浸润癌为2 0 / 2 7;宫颈腺癌中原位癌 1例CD44v6阴性 ;浸润癌 15例 ,CD44v6阳性表达 2 / 15。 (3)宫颈浸润鳞癌淋巴结转移阳性者CD44v6的灰度显著高于淋巴结转移阴性者 [(0 .30 8± 0 .0 2 1)vs (0 .2 73± 0 .0 31) ,P =0 .0 0 6 ]。CD44v6与宫颈鳞癌的临床分期及细胞分化程度无关。结论 :CD44v6在正常宫颈、CIN、宫颈浸润鳞癌中的阳性表达逐渐增加 ;CD44v6与宫颈鳞癌淋巴结转移相关 ;CD44v6阳性可能与宫颈腺癌的不良预后有关 ,其相关性需进一步研究。     

血清CD44及其拼接变异体sCD44v6测定对肺癌的诊治意义

目的：探讨测定血清中可溶性ＣＤ４４含量在肺癌中的临床意义。方法：用酶联免疫吸附试验（ＥＬＩＳＡ）检测４５例肺癌患者及１８例正常人血清中可溶性ＣＤ４４ｓ（ｓＣＤ４４ｓ）和可溶性ＣＤ４４ｖ６（ｓＣＤ４４ｖ６）的含量,结果：化疗前肺鳞癌和腺癌患者血清ｓＣＤ４４ｓ和ｓＣＤ４４ｖ６水平明显高于小细胞肺癌（ＳＣＬＣ）患者和正常组,差异非常显著;ＳＣＬＣ与正常人比较差异无显著性;非小细胞肺癌（ＮＳＣＬＣ）Ⅲ＋Ⅳ     

肺癌多种基因同步检测及临床相关性(诊断及预后)的研究

目的 :为检测非小细胞肺癌中多种基因的改变 ,并探讨其临床相关性 (诊断及预后 )。方法 :本研究用LSAB(labelledstreptavidinbiotin)法同步检测 10 4例非小细胞肺癌 (NSCLC)组织中抗癌基因p16,pRb及癌基因cy clinD1,cdk4和转移相关基因nm 2 3 H1,CD4 4v6表达。结果 :3 2 8%的鳞癌和 5 3 7%的腺癌不表达p16蛋白 ,腺癌明显高于鳞癌 (P <0 0 5 ) ;腺癌只有 14 6%完全不表达pRb蛋白 ,鳞癌不表达率为 3 6 2 % (P <0 0 5 ) ;5 7 7%的肿瘤只表达p16或pRb中的一项 ;3 2 7%的肿瘤两者都表达 ,但两者表达强度差异明显 ,9 6%的肿瘤两者均表达且表达强度一致 ;88 6%的肿瘤表达cdk4,在高分化鳞癌中表达率为 66 7% ,中分化鳞癌 96 3 % ,低分化鳞癌达10 0 % ,大约 70 %的肺癌中有cyclinD1表达 ,而正常粘膜中只有 2 0 %有表达 (P <0 0 0 0 1) ,表明非小细胞肺癌中cy clinD1的表达明显增高。在无淋巴结转移组 ,其nm 2 3的表达率高达 78 8% ,与有淋巴结转移组的表达率 2 1 9%相比 ,有非常显著性差异 (P <0 0 0 0 1) ;有淋巴结转移组 ,CD4 4v6的表达率高达 96 9% ,与无淋巴结转移的表达率相比 ,差异具非常显著性 (P <0 0 0 0 1)。结论 :①p16及pRb基因的表达在肺癌中明显减弱 ,均与非小细胞肺癌的组织学类型有关     

CD44v6、E-Cadherin表达与CNE-2Z-F1裸鼠移植瘤转移的关系

目的　探讨CD44v6、E -Cadherin表达与人鼻咽癌裸鼠移植瘤转移的关系。方法　分别将人鼻咽癌细胞克隆株F1在体外与鼠肺块共同孵育及胸内移植 ,然后将带瘤细胞肺块 (Ⅰ组 )和胸内瘤组织块 (Ⅱ组 )各行裸鼠皮下移植 ,并与瘤细胞悬液皮下移植瘤 (Ⅲ组 )比较 ,观察各组移植瘤转移特点。采用免疫组织化学技术检测各组移植瘤回复培养细胞CD44v6和E -Cadherin表达。结果　Ⅰ组和Ⅱ组皮下移植瘤的总转移率和淋巴结转移率均高于Ⅲ组 (其中ⅠvsⅢ ,P <0 .0 5) ;肺转移仅发生在Ⅰ组。这两组移植瘤细胞CD44v6表达水平明显增高 ,其阳性细胞数分别为 (79.7± 5.7) %、(74.1± 3.1 ) % ,第 3组为 (65.6± 4.31 ) %移植瘤转移率与CD44v6高表达密切相关 ;E -Cadherin阳性细胞分别为 (41 .7± 4.9) %、(43.8± 6.4) %和 (2 7.4± 4.9) % ,Ⅰ组、Ⅱ组与Ⅲ组之间比较 ,有显著差异 (P <0 .0 5)。结论　CD44v6的过表达和E -Cadherin功能障碍 ,可能在鼻咽癌侵袭转移中起一定作用。     

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas: Clinical and therapeutic features of 24 localized patients

Background: Peripheral B-cell lymphoma of the marginal zone (MALT, low-grade), presenting as localized, extranodal disease, usually affects the elderly. The gastrointestinal tract is the most frequently involved extranodal location, representing 70% of all MALT lymphomas. Recently, numerous other extranodal sites involved by MALT lymphomas have also been described.Patients and methods: From January 1990 to October 1995, 24 patients with untreated nongastrointestinal low-grade MALT lymphoma were submitted to treatments ranging from the local approach of radiotherapy and local -interferon (-IFN) administration to chemotherapy. The tumours were located in the lung (seven cases), conjunctiva (four cases), lachrymal gland and orbital soft tissue (four cases), salivary glands (three cases), skin (three cases), breast (two cases)' and thyroid (one case). All patients had low-grade stage IE tumours.Results: Chemotherapy was administered in 11 patients (six with lung, three with salivary gland, one with breast, and one with thyroid locations); radiation therapy was employed in seven patients (three with lachrymal gland, three with skin, and one with breast locations); local -IFN administration was administered in five patients (four with conjunctival, and one with lachrymal gland sites); and surgery was employed in one patient with a lung tumour. All patients achieved complete remissions; three local recurrences and two relapses in other sites were observed. The global five-year survival rate was 100% with a relapse-free survival rate of 79%.Conclusions: These data confirm the significant efficacy of different therapeutic approaches to specific sites inbes obtaining a good remission rate for nongastrointestinal localized low-grade MALT lymphomas.     

Hypofluorescent spots in indocyanine green angiography of peau d‘orange and fundus

Purpose. Hypofluorescent spots were seen inindocyanine green (ICG) angiography of peau dorangefundus in eyes with angioid streaks. Origin of the hypofluorescentspots were examined with attention to their correlationwith a peau dorange appearance of the central fundususing a computer-assisted image comparison system. Methods. ICG angiography was performed in 5 patientshaving peau dorange appearance of fundus using ascanning laser ophthalmoscope (SLO) and a digitalvideo-fundus camera. The same central fundus areas corresponding to hypofluorescent spots in an ICGangiogram were then digitally identified in afluorescein angiogram and in a red-free picture in all10 eyes of the 5 patients. Monochromatic lightobservation was also performed with a dark fieldobservation using a SLO to see subretinal orintrachoroidal pigment clumping. Results. In no patient, the areas identified withhypofluorescent spots did show relevant changes ina fluorescein angiogram or a red-free picture. SLOexamination revealed not perfusion defect at the sameareas. The dark field observation showed no pigmentclumping at the peripapillary and papillomacularbundle regions where hypofluorescent spots were seen.Conclusions: Hypofluorescent spots seen in ICGangiograms did not show exact consistency with peau dorange changes in their location and shape. Perfusion defects or blocking by pigments were not acause of hypofluorescent spots. The scatteredhypofluorescent spots were considered to be relevantwith irregular affinity of the fundus to ICG dye.     

Postnatal development of vascular β-adrenoceptor-mediated responses and the increase in the adrenaline content of the adrenal gland have a parallel time course

The present study was undertaken to analyse the relationship between postnatal development of vascular ₂-adrenoceptor-mediated responses and the content of adrenaline in the adrenal gland and its concentration in plasma. Dog saphenous vein tissue from newborn, two-weeks old and adult animals were either preloaded with ³H-noradrenaline (or ³H-adrenaline) to study prejunctional -adrenoceptor-mediated effects or mounted in organ baths to determine isoprenaline-induced relaxation of preparations contracted by phenylephrine to about 65010 of the maximum. The adrenal glands and samples of blood from the same animals were taken for estimation of adrenaline and noradrenaline.At birth, there were no -adrenoceptor-mediated effects pre- or postjunctionally. At two weeks, while the results at the prejunctional level were not significantly different from those obtained in newborns, at the postjunctional level there was a relaxant response to isoprenaline, which antagonised about 35010 of the previous contraction to 1.75 mol·l^–1 phenylephrine. In adults, isoprenaline (50 nmol·l^–1) increased by 24% tritium overflow evoked by electrical stimulation of tissues preloaded with ³H-noradrenaline but not that of tissues preloaded with ³H-adrenaline. On the other hand, propranolol (1 mol·l^–1) reduced by 21% the overflow of tritium evoked by electrical stimulation of tissues preloaded with ³H-adrenaline but not that of tissues preloaded with ³H-noradrenaline; postjunctionally, the maximal response to isoprenaline antagonised 70% of the previous contraction to 1.75 mol·l^–1 phenylephrine.At birth the catecholamine content of the adrenals was relatively low (2.9 ol·g^–1) and the adrenaline/noradrenaline ratio was 0.26; two weeks later, the catecholamine content was 14.5 mol·g-1and the adrenaline/noradrenaline ratio was 0.74; in adults, the catecholamine content was 24.5 mol·g^–1 and the adrenaline/noradrenaline ratio was 2.3. In plasma, the highest concentration of adrenaline was observed at birth (11.8 nmol·l^–1); two weeks later it was 5.5 nmol·l^–1 and in adulthood it fell to 3.1 nmol·l^–1.On the basis of these results, it is concluded that some link between the postnatal increase in adrenaline adrenal content and the development of ₂-adrenoceptor-mediated pre- and postjunctional effects may exist. Additionally it is suggested that circulating adrenaline may trigger the development of ₂-adrenoceptor-mediated responses as well as some hypertensive states occurring as a consequence of an overreactivity of the sympathoadrenal system. Correspondence to: S. Guimarães at the above address     

Drug effects on response duration differentiation I: differential effects of drugs of abuse

Rats were trained to respond under a response duration differentiation schedule in which responses on a lever were reinforced if lever press durations were greater than or equal to 1.00 s but were also less than 1.30 s. Dose-effect curves were generated for cocaine, methamphetamine, pentobarbital, phencyclidine, delta-9-tetrahydrocanninabol (⁹-THC), and morphine. All drugs produced dose-dependent decreases in accuracy (the percentage of total response durations that were reinforced); however, the degree to which changes in accuracy were accompanied by changes in response rates varied among drugs. Pentobarbital and morphine affected primarily longer (> 1.3 s) response durations, phencyclidine and ⁹-THC affected primarily shorter response durations, whereas cocaine and methamphetamine affected both shorter and longer response durations. High doses of methamphetamine and cocaine increased the dispersion of response duration distributions with increasing dose, whereas higher doses of pentobarbital, ⁹-THC and morphine did not increase dispersion of response duration distributions as much. These data show that behavior under this novel schedule is differentially sensitive to a number of pharmacologic manipulations, and that the schedule can provide a useful addition to the analysis of drug effects upon behavior.