Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18

Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.     

Chronic pelvic pain: Psychological features and laparoscopic findings

One hundred three consecutive patients referred for treatment of chronic pelvic pain underwent MMPI testing, and 60 had diagnostic laparoscopy. A physical cause for the pain was found in 45 (75%) of the 60. However, three fourths (34) of patients with an organic cause for the pain also had evidence of psychopathology on the MMPI. Reassurance and education as to the role of stress in causing or exacerbating pain complaints appeared helpful. Most patients improve without major surgery.     

肩关节上关节囊重建治疗肩袖损伤适应证和移植物处理方法研究进展

目的对肩关节上关节囊重建治疗肩袖损伤适应证和移植物处理方法的研究进展进行综述。方法广泛查阅近年来国内外有关肩关节上关节囊重建治疗肩袖损伤的文献，并进行总结分析。结果肩关节上关节囊重建可以有效恢复肩关节上方稳定性，其手术适应证包括不可修复巨大肩袖撕裂、巨大肩袖撕裂合并肩关节假性麻痹、肩袖分层撕裂以及中或大的肩袖撕裂合并肩袖严重退变。为了获得较好的腱骨愈合以及降低移植物远期再撕裂率，必须选择合适厚度的移植物，并以适当的强度固定移植物并恢复其连续性。结论肩关节上关节囊重建的手术应用已发展至上关节囊加强重建，手术适应证从肩袖实质性巨大缺损扩展至肩袖严重退变。移植物处理是上关节囊重建手术成功的关键。     

计算流体力学在组织工程中的应用进展

目的综述计算流体力学（computational fluid dynamics，CFD）在组织工程中的应用进展。方法广泛查阅 CFD 应用于组织工程的相关文献，主要对 CFD 用于生物反应器设计改良或优化、模拟体外组织再生过程中的流体动力学和细胞生长动力学等方面进行综述。结果CFD 的模拟预测能力可为生物反应器的设计优化和体外组织工程组织培养提供重要的指导作用，且结合实验研究能进一步提高模型预测结果的准确性。结论CFD 作为新兴和有效的研究工具，已在组织工程中展现出独特优势并取得显著进展，但更全面、准确地模拟组织再生全过程仍需进一步研究。     

Alpha1-adrenoceptor-mediated inhibition of cellular cAMP accumulation in neonatal rat ventricular myocytes

Summary We studied adrenergic regulation of cellular cAMP in neonatal rat ventricular myocytes. Since CAMP content depends on synthesis, breakdown and egress, the contribution of each of these mechanisms was assessed. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, cAMP accumulation stimulated by the -adrenoceptor agonist (–)-isoprenaline was diminished when the mixed + adrenoceptor agonist (–)-noradrenaline was coincubated with (–)-isoprenaline. Moreover, adenylyl cyclase activation stimulated by (–)-isoprenaline was decreased by (–)-noradrenaline and by the selective a₁-adrenoceptor agonists (–)-phenylephrine and methoxamine, suggesting that -adrenoceptor agonism regulates CAMP metabolism through its effect on the synthetic pathway. Evidence for ₁-adrenoceptor mediation of this response was enhancement of (–)-noradrenaline-induced cAMP generation by the selective ₁-adrenoceptor antagonist terazosin (10 nmol/l). The selective ₂-adrenoceptor antagonist yohimbine (10 nmol/l) had no effect. The ₁-adrenoceptor mediated depression of (–)-isoprenaline-stimulated CAMP generation and adenylyl cyclase activation was prevented by terazosin and in separate experiments markedly enhanced by pertussis toxin pretreatment, suggesting involvement of a guanine-nucleotide regulatory protein in this process.Occupation of the ₁-adrenoceptor by (–)-noradrenaline did not accelerate the rate of CAMP breakdown in the absence of phosphodiesterase inhibition. Furthermore, there was no enhancement of total phosphodiesterase activity by (–)-noradrenaline in the presence of (–)-propranolol. By contrast, pertussis toxin pretreatment augmented phosphodiesterase activity. Neither pertussis toxin nor (–)-noradrenaline increased CAMP egress.We conclude that in rat neonatal cardiac myocytes agonist occupation of the ₁-adrenoceptor inhibits -adrenoceptor stimulated CAMP accumulation most likely by coupling to a guanine nucleotide inhibitory protein.Supported by a grant from the Department of the Veterans Affairs Research Service and Program Project Grant HL 25847 from the National Heart, Lung and Blood Institute     

尼龙1010／6及尼龙1010／66动态力学分析

通过动态力学参数温度谱,研究了尼龙１０１０／６、尼龙１０１０／６６两个共聚物系列的动态力学参数与组成的关系。研究表明尼龙１０１０／６、尼龙１０１０／６６在测试温度范围内出现三个明显的松驰转变：α、β、γ,其中各共聚物的β、γ松驰温度相差不大,而α松驰温度随组成改变有明显改变。一般均聚物的α松驰温度较高,共聚物的α松驰温度均低于均聚物,二个系列以尼龙１０１０／６（２９．８／７０．２）、尼龙１０１０／     

Assessment of hepatic graft injury by graft effluent in rodents: N-acetyl-β-glucosaminidase and type III procollagen peptide

We studied the significance of N-acetyl--glucosaminidase (-NAG) and type III procollagen peptide (P-III-P) in the effluent of rodent hepatic grafts. After total hepatectomy, the livers were preserved in chilled, lactated Ringer's solution and then divided into five groups (n=10 each): group 1, 4 h preservation only; group 2, 4 h preservation and rewarming; group 3, 6 h preservation only; group 4, 6 h preservation and rewarming; and group 5, minimal preservation only. The -NAG of groups 2 and 4 was significantly higher than that of groups 1 and 3 (0.98±0.5 U/l vs 0.21±0.12 U/l; P<0.01 and 1.76±0.67 U/l vs 0.38±0.25 U/l, respectively; P<0.01), while that of group 4 was significantly higher than that of group 2 (1.76±0.67 U/l vs 0.98±0.50 U/l; P<0.05). The P-III-P of group 4 was significantly higher than that of group 2 (0.133±0.008 U/ml vs 0.110±0.015 U/ml; P<0.01). We conclude that -NAG is a novel parameter of parenchymal and nonparenchymal cells, while P-III-P reflects the integrity of the hepatic sinusoidal extracellular matrix.     

Effects of drugs of abuse on acquisition of behavioral chains in squirrel monkeys

The acute effects of various drugs of abuse on the acquisition of chains of behavior were assessed in squirrel monkeys trained to respond on three keys for food. Each new session the monkeys acquired a different four-response chain by responding sequentially on three keys in the presence of four different stimuli. Incorrect responses inactivated the keys and darkened the chamber for 10 s (time-out). Dose-effect curves were obtained by administering the drugs intramuscularly before the session and recording their effects on the rate and accuracy of responding. Cocaine,d-amphetamine, and ⁹-tetrahydrocannabinol all decreased the accuracy and rate of responding within the dose range of 0.56–3 mg/kg. The highest dose of morphine tested (3 mg/kg) produced parallel decreases in the accuracy and rate of responding in some monkeys but had no effect at lower doses. These drugs decreased within-session accuracy though clearly acquisition did occur, but high doses of caffeine (30 and 56 mg/kg) prevented acquisition and recovery of performance and, furthermore, at 30 mg/kg these effects were observed in the absence of decreases in the rate of responding. The drugs of abuse tested all produced dose-related decreases in both the accuracy and rate of responding, and the decreases in accuracy were primarily observed only at doses that also decreased response rates. Therefore, based on these results from nonhuman primates each of these drugs has the potential to alter learning particularly when doses that disrupt other behaviors are administered.     

Alpha adrenoceptors in rat brain: Direct identification with prazosin

Summary Tritiated prazosin was used to characterize high affinity binding sites with characteristics similar to ₁ adrenoceptors in rat brain membranes. These sites were compared with ₂ adrenoceptors labeled with tritiated clonidine. The prazosin sites had an association constant of 2 nM^–1 and bound the ligand optimal around pH 7.0. The density of the sites was 300 fmoles per mg of protein; the half time of dissociation of prazosin was 7 min at 30° C. The order or potencies of agonists, determined from binding-inhibition experiments with labeled prazosin, was: naphazoline > clonidine > adrenaline > noradrenaline > phenylephrine > -methylnoradrenaline > dophamine. The order of potencies of antagonists was: prazosin > phenoxybenzamine > phentolamine > clozapine > yohimbine. Sodium ions and divalent cations as well as guanyl nucleotides have little or no effect on the binding of the labeled antagonist. This is in contrast to the binding of the labeled agonist clonidine (Glossmann and Presek, 1979a, 1979b). Labeled prazosin may be a useful tool to characterize ₁ adrenoceptors.This is part of the thesis of R. H. to be presented to the Fachbereich Humanmedizin, Justus Liebig-Universität Giessen, in partial fulfillment of the requirements for a Doctor of Medical Science degreee     

Nogo-66受体在脂质筏中的定位

目的 探讨Nogo-66受体（NgR）存神经元胞膜脂质筏中的定位。方法 利用免疫荧光双标法检测NgR和脂质筏特异标志物穴蛋白（Cavcolin）在培养的小脑颗粒神经元上的表达．并用Wcstcrn blot法检测以去垢剂法提取的脂质筏中NgR的表达。结果 免疫荧光双标显示NgR和Cavcolin的表达部化．Western blot分析发现脂质筏中NgR的表达为阳性。结论 在小脑颗粒神经元胞膜脂质筏中有NgR的表达．提示脂质筏有可能促进NgR的信号转导。