67Ga心肌炎症显像对小儿病毒性心肌炎的诊断价值

目的 :探讨6 7Ga心肌显像对小儿病毒性心肌炎 (VMC)诊断的临床价值。方法 :静脉注射6 7Ga 枸橼酸盐 ,48h、72h后开始显像 ,观察心脏部位放射性浓聚情况 ,并计算心 /肺 (H/L)指数 ,根据H/L指数判断心肌炎性病变的严重程度 (H/L指数 >1.2为阳性 )。结果 :78例病毒性心肌炎患儿中 ,50例阳性 (占 64% ) ,其中急性期阳性率为 84% ,恢复期阳性率为 50 % ,慢性期为 2 9% ,急性期阳性率明显高于恢复期和慢性期 (P<0 .0 5)。结论 :心肌6 7Ga放射性浓聚与心肌炎病变程度呈正相关 ,直接反映了病变心肌的炎症反应情况 ,对诊断VMC有较高的临床价值 ,并对VMC治疗、预后有指导作用     

青年人群血清甲_3型流感抗体检测和流行株的抗原性分析

采集４５０例战士血清标本，分别用国家代表株甲３／济防／１５／９０（Ｈ３Ｎ２）和甲３／北京／３２／９２（Ｈ３Ｎ２）作血清血凝抑制抗体测定，青年对甲３型抗体阳性率为６０％～６７％，其ＧＭＴ为３４～４５。１９９４～１９９５年两年中在军营人群中分离到３株Ｈ３Ｎ２毒株流行株，分别应用国际、国家和地方代表株作抗原性分析，证明流行株与它们之间抗原性有明显差异。本文分离到的３株流行株均上送国家流感中心鉴定，证实为Ｈ３Ｎ２亚型毒株。     

Down-regulation of rat β-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [H]CGP-12177 binding reveals rapid (24 hour) modulation

Desipramine (DMI, 15 mg/kg, s.c.) decreased [³H]CGP-12177-labelled cortical β-adrenoceptor density (B_max) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the β-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of β-adrenoceptor B_max (−15%; p<0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [³H]CGP-12177-labelled β-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the B_max of [³H]ketanserin-labelled 5-HT_2A receptors on acute treatment. These results show that β-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.     

人肺癌细胞转录因子--C/EBP和HMG样蛋白的EMSA检测

目的：检测人肺癌细胞中是否存在与Na^ /H^ 交换蛋白-1（NHE-1）基因转录相关的重要转录因子--C/EBP和HMG样蛋白。方法：采用电泳迁移率改变分析法（EMSA）检测人肺癌细胞株核蛋白中C/EBP和HMG样蛋白的表达及其水平。结果：EMSA检测到A549细胞和转染NHE-1反义载体的A549细胞均有转录因子C/EBP和HMG样蛋白的表达，且后者表达水平高于前者；采用50倍未标记的片段能完全抑制相应转录因子与^32P标记的相同片段的结合。结论：A549细胞核蛋白中存在能与C/EBP结合序列和Poly(dA：dT)区结合的转录因子，即C/EBP和HMG样蛋白，后者的表达水平高于前者。特异性竞争抑制试验表明外源性特异DNA片段能抑制相同片段与转录因子的结合。     

Investigation of the anti-complement agents, FUT-175 and K76COOH, in discordant xenotransplantation

Abstract: We examined whether hyperacute rejection (HAR) of a discordant xenograft in a nonhuman primate model could be inhibited by the anticomplement agents, FUT-175 (FUT) and K76COOH (K76). The inhibitory effect of FUT and K76 on baboon sera was studied in vitro by i) complement-mediated hemolysis of sheep erythrocytes (by measuring serum CH50) and ii) cytotoxicity to cultured pig kidney (PK15) cells. The in vivo administration of FUT (at 0.2–25 mg/kg/h i.v. continuously) and K76 (50 mg/kg i.v. bolus) allowed evaluation of the serum levels of these drugs. Both FUT and K76 inhibited serum CH50 in a concentration-dependent manner. An enhanced effect was obtained by combining K76 with FUT therapy. High concentrations of FUT (>10^-4 M) and K76 (>10³ μxg/ml) were necessary to suppress serum CH50 to <5% of the normal level. However, PK15 cytotoxicity remained at >50% in the presence of i) 10^-4 M of FUT, ii) 10³ μg/ml of K76, and iii) 10^-6 M of FUT + 10³ μg/ml of K76. Pig heart transplantation (HTX) was performed in two baboons receiving FUT (1 mg/kg/h i.v. continuously) and K76 (at 200 mg/kg ×1 or 400 mg/kg + 200 mg/kg × 2 i.v, respectively). Cytotoxicity of the serum to PK15 cells at the time of HTX showed 39% and 1% cell death, respectively, in these two baboons, and the CH50 level was 1% (of control level) and 0%, respectively. Graft survival was 4.5 hours and 10 hours (with death of the baboon), respectively (compared with a mean of 29 minutes in control experiments). Both excised grafts showed typical features of hyperacute rejection. Immunopathological studies revealed deposition of C1q, C3d, C6, properdin, and Factor B, demonstrating that complement activation was not fully inhibited by FUT and K76. We conclude that i) FUT and K76 are indeed potent complement inhibitors, ii) the dosages of FUT and K76 necessary to suppress complement-mediated injury cannot be extrapolated from previously reported data obtained from serum CH50 levels, and iii) higher (possibly toxic) dosages will be required to inhibit complement activation completely. It seems unlikely that HAR will be prevented by these drugs alone, although they may be beneficial when combined with other forms of therapy.     

Proteolytic Processing Mechanisms in the Biosynthesis of Neuroendocrine Peptides: The Subtilisin-like Proprotein Convertases

The recent discovery of a novel family of precursor processing endoproteases has greatly accelerated progress in understanding the complex mechanisms underlying the maturation of prohormones, neuropeptides, and many other precursor-derived proteins. At least six members of this family have been found thus far in mammalian species, several having alternatively spliced isoforms, and related enzymes have been identified in many invertebrates, including molluscs, insects, nematodes, and coelenterates. The proprotein convertases are all dependent on calcium for activity and all possess highly conserved subtilisin-like domains with the characteristic catalytic triad of this serine protease (ordered Asp, His, and Ser along the polypeptide chain). Two members of this family, PC2(SPC2) and PC1/PC3(SPC3), appear to play a preeminent role in neuroendocrine precursor processing. Both convertases are expressed only in the brain and in the extended neuroendocrine system, while another important family member—furin/PACE (SPC1)—is expressed more ubiquitously, in almost all tissues, and at high levels in liver. SPC2 and SPC3 exhibit acidic pH optima and other properties which enhance their activity in the acidic, calcium-enriched environment of the dense-core secretory granules of the regulated pathway in neuroendocrine cells, while furin has a neutral pH optimum and is localized predominantly to the trans Golgi network where it is retained by a C-terminal transmembrane domain. Furin processes a wide variety of precursors in the constitutive pathway, such as those of growth factors, receptors, coagulation factors, and viral glycoproteins. Recent findings on the processing of proopiomelanocortin, proinsulin, proglucagon, and several other neuroendocrine precursors by SPC2 and SPC3 are discussed, along with information on the structure, properties, evolution, developmental expression, and regulation or the convertases. An inherited defect in the fat/fat mouse which affects the processing of proinsulin, and probably also many other prohormones, due to a point mutation in carboxypeptidase E has recently been identified and has begun to provide new insights into the functional integration of the individual processing steps.     

Diagnostik und Therapie von Harnstoffzyklusdefekten

Zusammenfassung Fragestellung: Es werden die Verl?ufe von 8 Patienten mit St?rungen der Harnstoffsynthese [Carbamylphosphatsynthetasemangel (4), Citrullin?mie (2) und Argininosuccinatlyasemangel (2) ] beschrieben. Methode/Therapieprinzipien: Akuttherapie: Na-Benzoat und Arginin i. v., dazu Peritonealdialyse und/oder H?modiafiltration. Lanfristige Therapie: proteinreduzierte Ern?hrung, Substitution essentieller Aminos?uren, Na-Benzoat bzw. Na-Phenylbutyrat oral, Substitution von verzweigtkettigen Aminos?uren. Ergebnisse: Sp?testens 3 Tage post partum entwickelte sich nach initialer Alkalose ein hyperammon?misches Koma mit Hirn?dem, das zu deutlichen Residualsch?den führte. Vier Patienten verstarben zwischen der 2. Lebenswoche und dem 4. Lebensjahr aus unterschiedlichen Gründen. Hyperammon?mien traten bei allen Patienten auf und lie?en sich konservativ beherrschen. Na-Phenylbutyrat verursachte weniger gastrointestinale Nebenwirkungen als Na-Benzoat, verzweigtkettige Aminos?uren hatten einen positiven Effekt. Ein Patient wurde vom 1. Lebenstag an medikament?s behandelt, die Entwicklung verlief altersgerecht. Schlu?folgerung: Die Symptome Alkalose, respiratorische Insuffizienz und eine schnelle Verschlechterung des Allgemeinzustands bei Neugeborenen sollten an einen Harnstoffzyklusdefekt denken lassen. Medikament?se Therapie und die Kombination aus Peritoneal- und H?modiafiltration sind prim?r lebenserhaltend. Deutliche Residualsch?den sind die Regel, die überlebensprognose ist eingeschr?nkt. Na-Phenylbutyrat hat weniger Nebenwirkungen als Na-Benzoat. Therapiebeginn vor dem neonatalen Hirn?dem kann Komplikationen verhindern.      

New Potent Azomethine Prodrugs of the Histamine H3-Receptor Agonist (R)-α-Methylhistamine Containing a Heteroarylphenyl Partial Structure

The therapeutic value of histamine H₃-receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H₃-receptor agonist (R)-α-methyl-histamine ( 1 ) a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1 , and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino](1H-pyrrol-2-yl)methyl]phenol ( 8c ), the 2-furanyl analogue 8d , and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H₃-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.     

球形幽门螺杆菌生物学性状及蛋白产物研究球形Hp系列研究之二

目的：研究球形幽门螺杆菌生物学性状和蛋白产物发生的改变。方法：通过延长培养时间和亚抑菌浓度抗生素－－灭滴灵的作用，分别获得两类球形幽门螺杆菌（Ｈｐ）。结果：两种不利于Ｈｐ生长的环境在引起Ｈｐ发生球变的同时，每毫升菌落形成单位（ＣＦＵ／ｍｌ）减少，尿素酶活性降低。结论：球形Ｈｐ尿素酶活性低下，且在常规培养基上不能生长。抗生素的作用比延期培养更快使Ｈｐ发生球形变异。聚丙烯酰胺凝胶电泳蛋白质条带分析发现抗生素诱变的球形Ｈｐ与正常形态Ｈｐ基本相似，与延期培养的Ｈｐ明显不同。     

ABH- und Lewis-Antigene der Trachealdrüsen

Zusammenfassung In 23 Sektionsfällen, bei denen am Leichenblut der erythrocytäre Typ Le (a–b–) festgestellt worden war, wurden an paraffineingebetteten Trachealwandproben immunhistochemische Studien durchgeführt. Die Antigendarstellungen erfolgten nach der indirekten Immunperoxidasemethode mit monoklonalen Antikörpern gegen Le^a, Le^b, A und B als primären Antikörpern; das H-Antigen wurde mit UEA 1 dargestellt. Das Markierungsverhalten der mukösen Drüsen für die ABH-Antigene erlaubte eine eindeutige Differenzierung zwischen Sekretoren und Nonsekretoren. Das Lewis-Markierungsverhalten war in 11 Fällen mit demjenigen Lewis-positiver Individuen identisch. Statistische Betrachtungen legen nahe, daß es sich bei dieser Gruppe tatsächlich um Lewis-positive Individuen handelt, deren erythrocytäre Lewis-Merkmale im gealterten Leichenblut nicht erfaßt wurden. Die übrigen 12 Fälle zeigten ein völlig anderes immunhistochemisches Bild: a) Die Sekretoren (n=9) waren für Le^a vollständig negativ; Le^b war in einem Falle nicht, in den übrigen Fällen innerhalb muköser Epithelien in minimaler Quantität und atypischer, granulärer Verteilung nachweisbar. b) Nonsekretoren (n=3) wiesen umgekehrt bei völliger Negativität für Le^b abortive Markierungen für Le^a auf. Diese Beobachtungen, die mit bekannten serologischen Befunden an den Sekreten gut übereinstimmen, sprechen dafür, daß auch in Abwesenheit des Le-Gens in geringer Menge Lewis-Antigene synthetisiert und sezerniert werden können: Möglicherweise kodiert das Allel le eine -4-l-Fucosyltransferase geringer Effizienz.