BACKGROUND & AIMS: :Human class II MHC Ag are a family of cell surface glycoproteins. Their constitutive expression is limited to B lymphocytes and thymic epithelial cells. In many other cells their expression can be induced by IFN-gamma. Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes. In the DRA promoter, one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 (NF-X2) binds. Here, we present the isolation and characterization of the full-length cDNA clone encoding NF-X2. This cDNA clone was isolated by expression cDNA cloning, and encodes the human c-Jun protein, which together with c-Fos forms the heterodimeric activator protein-1 transcription complex. Whereas c-Fos/c-Jun heterodimers do not exist in B cells, they form and bind to the X2-box in class II nonexpressing cells. Thus, c-Fos/c-Jun heterodimers might contribute to the repression of DRA gene expression.

背景与目标： ：人类II类MHC Ag是细胞表面糖蛋白家族。它们的组成型表达仅限于B淋巴细胞和胸腺上皮细胞。在许多其他细胞中，它们的表达可以被IFN-γ诱导。保守的上游启动子序列调节II类基因的这种组织特异性表达。在DRA启动子中，这些顺式作用调控基元之一是X2-box，其与核因子X2（NF-X2）结合。在这里，我们介绍了编码NF-X2的全长cDNA克隆的分离和表征。该cDNA克隆通过表达cDNA克隆进行分离，并编码人c-Jun蛋白，该蛋白与c-Fos一起形成异二聚激活蛋白-1转录复合体。尽管B细胞中不存在c-Fos / c-Jun异二聚体，但它们在II类非表达细胞中形成并与X2-box结合。因此，c-Fos / c-Jun异二聚体可能有助于抑制DRA基因表达。

BACKGROUND & AIMS: PURPOSE:To assess the technical feasibility, thrombogenicity, and biocompatibility of a new biodegradable poly-L-lactic acid (PLLA) anastomotic stent. METHODS:A polytetrafluoroethylene bifurcated graft was implanted in 17 pigs through a midline abdominal incision. After transverse graft incision, 17 316L stainless steel stents and 17 PLLA stents were randomly implanted at both iliac anastomotic sites and deployed with a 6-mm balloon under direct vision without angiography. Intended follow-up was 1 week in 6 pigs receiving oral acetylsalicylic acid (ASA) and in 7 pigs receiving ASA/clopidogrel; 4 pigs receiving ASA/clopidogrel were followed for 6 weeks. At the end of the study, the segments containing the stents were surgically explanted and processed for histology to measure the mean luminal diameter, intimal thickness, and the vascular injury and inflammation scores. RESULTS:Initial technical success of stent placement was achieved in all animals without rupture of the suture. Two pigs died (unrelated to the stent) at 3 days after operation (1 in groups A and B). At 1 week, all PLLA stents showed thrombotic occlusion with the use of ASA alone. In contrast, all PLLA stents remained patent with concurrent administration of ASA/clopidogrel. All metal stents were patent regardless of the antiplatelet regimen. The mean luminal diameter of patent PLLA stents (4.13+/-0.17 mm) was comparable to metal stents (4.27+/-0.35 mm, p=0.78) at 1 week, but significantly diminished at 6 weeks (3.21+/-0.44 versus 4.19+/-0.18 mm, p=0.005). Histological analysis showed no signs of excessive recoil. PLLA stents induced a higher inflammation score (1.79+/-0.56) and more intimal hyperplasia (0.34+/-0.11 mm) compared to metal stents [1.27+/-0.44 mm (p<0.001) and 0.18+/-0.04 mm (p=0.006), respectively] at 6 weeks. Vascular injury was comparable between PLLA and metal stents. CONCLUSION:Biodegradable PLLA stents showed higher thrombogenicity and reduced patency compared to metal stents during early follow-up. Although ASA and clopidogrel prevented thrombotic occlusion, the increased inflammatory response and neointima formation remain major concerns of PLLA stents. A solution to this problem might be the incorporation of anti-inflammatory drugs into the PLLA stent.

背景与目标： 目的：评估新型可生物降解的聚-L-乳酸（PLLA）吻合支架的技术可行性，血栓形成性和生物相容性。
方法：通过腹部中线切口将聚四氟乙烯分叉移植物植入17只猪。横向移植后，将17个316L不锈钢支架和17个PLLA支架随机植入两个both吻合部位，并在不进行血管造影的情况下在直视下用6毫米球囊展开。预期的随访结果是：6头接受口服乙酰水杨酸（ASA）的猪和7头接受ASA /氯吡格雷的猪。对4只接受ASA /氯吡格雷的猪进行了6周的随访。在研究结束时，将包含支架的节段进行外科手术切除并进行组织学处理，以测量平均腔直径，内膜厚度以及血管损伤和炎症评分。
结果：在所有动物中均未发生缝线破裂的情况下，支架植入取得了初步的技术成功。手术后3天有2头猪死亡（与支架无关）（A和B组为1只）。在第1周，仅使用ASA时，所有PLLA支架均显示血栓闭塞。相反，所有PLLA支架在同时使用ASA /氯吡格雷的情况下仍保持专利。无论抗血小板方案如何，所有金属支架均已获得专利。专利PLLA支架的平均腔直径（4.13 /-0.17 mm）在1周时可与金属支架（4.27 /-0.35 mm，p = 0.78）相媲美，但在6周时显着减小（3.21 // 0.44对4.19 /-） 0.18毫米，p = 0.005）。组织学分析显示没有过度后坐的迹象。与金属支架[1.27 /-0.44 mm（p <0.001）和0.18 /-0.04 mm（p = 0.006）相比，PLLA支架引起更高的炎症评分（1.79 /-0.56）和更多的内膜增生（0.34 /-0.11 mm）。分别]在6周。 PLLA和金属支架之间的血管损伤相当。
结论：在早期随访中，与金属支架相比，可生物降解的PLLA支架显示出更高的血栓形成性和通畅性降低。尽管ASA和氯吡格雷预防了血栓闭塞，但炎症反应和新内膜形成的增加仍然是PLLA支架的主要关注点。解决该问题的方法可能是将抗炎药掺入PLLA支架中。

BACKGROUND & AIMS: :A new inhibitor of human immunodeficiency virus (HIV) has been isolated and purified to homogeneity from the seeds and fruits of the Momordica charantia. This compound, MAP 30 (Momordica Anti-HIV Protein), is a basic protein of about 30 kDa. It exhibits dose-dependent inhibition of cell-free HIV-1 infection and replication as measured by: (i) quantitative focal syncytium formation on CEM-ss monolayers; (ii) viral core protein p24 expression; and (iii) viral-associated reverse transcriptase (RT) activity in HIV-1 infected H9 cells. The doses required for 50% inhibition (ID50) in these assays were 0.83, 0.22 and 0.33 nM, respectively. No cytotoxic or cytostatic effects were found under the assay conditions. These data suggest that MAP 30 may be a useful therapeutic agent in the treatment of HIV-1 infections. The sequence of the N-terminal 44 amino acids of MAP 30 has been determined.

背景与目标： ：已从苦瓜种子和果实中分离出一种新的人类免疫缺陷病毒（HIV）抑制剂并将其纯化至同质。该化合物MAP 30（Momordica抗HIV蛋白）是大约30 kDa的碱性蛋白。它通过以下方式表现出对无细胞HIV-1感染和复制的剂量依赖性抑制作用：（i）在CEM-ss单层上的定量局灶性合胞体形成； （ii）病毒核心蛋白p24表达； （iii）HIV-1感染的H9细胞中的病毒相关逆转录酶（RT）活性。在这些试验中，抑制50％（ID50）所需的剂量分别为0.83、0.22和0.33 nM。在测定条件下未发现细胞毒性或细胞抑制作用。这些数据表明，MAP 30可能是治疗HIV-1感染的有用治疗剂。已经确定了MAP 30的N-末端44个氨基酸的序列。

BACKGROUND & AIMS: BACKGROUND:A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS:Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS:(1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. CONCLUSIONS:Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.

背景与目标： 背景：α-1肾上腺素受体亚型（高，低）的新型分类被应用于人类良性前列腺肥大（BPH）组织。
方法：使用3H-吡唑嗪通过放射性配体结合测定法检查人的BPH标本，并将这些数据与术前治疗进行比较。
结果：（1）Scatchard分析显示高亲和力位点（Kd：27.18 /-6.41 pM; Bmax：9.29 /-0.98 fM / mg蛋白;平均值/-SE）为alpha 1H，低亲和力位点（Kd ：prazosin：α1L亚型：4088.0 /-744.34 pM，Bmax：140.81 /-19.98 fM / mg蛋白）。 （2）在未经治疗的组（n = 5），α1受体阻滞剂组（n = 5）和抗雄激素组（n = 5）中，Kd和Bmax的差异无显着性，二者均为α1-高亲和力或α1-低亲和力亚型。 （3）以上两种肾上腺素受体亚型的苯氧基苯甲胺的pKi值不同。斯卡查德分析表明，在存在1 microM苯氧基苯扎明的情况下，α1高亲和力结合位点消失了，在存在1 microM苯氧基苯扎明的情况下，Kd和Bmax值几乎与两种亚型的α1低亲和力位点相同。 。
结论：根据对Prazosin的亲和力，人类BPH组织同时具有alpha 1H-和alpha 1L-肾上腺素受体亚型，只有一定浓度的苯氧基苯扎明才能完全抑制alpha 1H亚型。用α1受体阻滞剂治疗可能不会改变前列腺组织中α1肾上腺素能受体的状况。

BACKGROUND & AIMS: :Descriptions of primary HIV-1 infection have so far been based on Caucasians living in industrialized nations. Due to studies of leptospirosis in the predominantly black population of Barbados, serum was available for patients admitted with acute febrile illnesses to the Queen Elizabeth Hospital (QEH). By searching the medical records of 510 adult patients with known HIV-1 infection we identified 10 patients who had stored serum from an admission for an acute febrile illness that predated or coincided with their first HIV-1-positive test. Serological testing confirmed primary HIV-1 infection in 9 and was suggestive in the 10th patient. The clinical features of these 10 patients were in keeping with previous descriptions of primary HIV-1 infection but differed from leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. The findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established. :A retrospective review was conducted of the medical records of 510 HIV-1-positive adult patients who had attended the Queen Elizabeth Hospital (QEH) to determine whether any had been admitted for an illness compatible with a diagnosis of primary HIV-1 infection. A serum bank, created from patients who had been admitted with acute febrile illnesses and investigated for leptospirosis, provided serological evidence for primary HIV-1 infection in 10 patients. Serological testing of the serum samples confirmed primary HIV-1 infection in nine patients and was suggestive in the tenth. The clinical features of the 10 patients fit the earlier descriptions of primary HIV-1 infection, but differed from the leptospirosis cases seen at the QEH. One patient died during his seroconversion illness and another died 3 months after seroconversion. These findings suggest that severe primary HIV-1 infection could be a relatively uncommon occurrence, that the condition may be misdiagnosed, and that cases may not occur until the AIDS epidemic is established.

背景与目标： ：到目前为止，主要针对HIV-1感染的描述都是基于生活在工业化国家中的高加索人。由于对巴巴多斯主要是黑人人群的钩端螺旋体病进行了研究，因此伊丽莎白女王医院（QEH）接受了急性发热性疾病的患者可获得血清。通过搜索510例已知HIV-1感染的成年患者的病历，我们确定了10例在首次发热HIV-1阳性测试之前或与其同时发生的急性发热疾病患者入院时就储存了血清的患者。血清学检查证实了9例原发性HIV-1感染，并提示第10例患者。这10例患者的临床特征与原发性HIV-1感染的先前描述相符，但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡，另一名患者在血清转化后3个月死亡。研究结果表明，严重的原发性HIV-1感染可能是相对罕见的事件，该病可能被误诊，只有在AIDS流行之前，病例才可能发生。
：回顾性分析了510例曾在伊丽莎白女王医院（QEH）住院的HIV-1阳性成年患者的病历，以确定是否有人因与原发性HIV-1感染诊断相符的疾病而入院。由被接纳患有急性发热性疾病的患者创建的血清库，并研究了钩端螺旋体病，为10例患者的原发性HIV-1感染提供了血清学证据。血清样本的血清学检测证实了9名患者的原发性HIV-1感染，而第十名患者则具有启发性。这10例患者的临床特征符合原发性HIV-1感染的早期描述，但与QEH所见的钩端螺旋体病病例有所不同。一名患者在血清转化疾病中死亡，另一名患者在血清转化后3个月死亡。这些发现表明，严重的原发性HIV-1感染可能是相对罕见的事件，可能会误诊该病，并且直到艾滋病流行才可能发生。

BACKGROUND & AIMS: :CD5 (Ly-1) B cells are a minor subpopulation in mouse spleen and are thought to be responsible for the production of natural autoantibodies to bromelain-treated autologous erythrocytes (Br-RBC). Here it is shown that substantial numbers of conventional, CD5-negative, splenic B cells also secrete these antibodies in CBA and (NZB x NZW)F1 mice, whereas in NZB and BALB/c mice they are all produced by the CD5 B-cell population. However, stimulation with bacterial lipopolysaccharide in vivo preferentially activates the CD5 B-cell group to anti-Br-RBC antibody secretion.

背景与目标： ：CD5（Ly-1）B细胞是小鼠脾脏中的次要亚群，被认为负责产生与菠萝蛋白酶处理的自体红细胞（Br-RBC）的天然自身抗体。在此表明，大量常规的CD5阴性脾脏B细胞也在CBA和（NZB x NZW）F1小鼠中分泌这些抗体，而在NZB和BALB / c小鼠中，它们都是由CD5 B细胞产生的人口。但是，在体内用细菌脂多糖刺激可优先激活CD5 B细胞基团以分泌抗Br-RBC抗体。

BACKGROUND & AIMS: :Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.

背景与目标： ：缺乏1型甾体5α-还原酶的雌性小鼠的窝产仔数减少。纯合缺陷型雌性的平均产仔数为2.7头，而野生型对照为8.0头。在突变动物中，卵子发生，受精，着床和胎盘形态正常。胎儿丢失发生在妊娠10.75至11.0天之间，与胎盘雄激素产生的中期妊娠激增和野生型小鼠蜕膜中5α-还原酶1型表达的诱导相称。在淘汰的第9天，雄烯二酮和睾丸激素的血浆水平升高了2至3倍，而在早期和中期妊娠期，雌二醇水平长期升高了2至3倍。在突变小鼠中，雌激素受体拮抗剂或芳香化酶抑制剂的使用可以逆转高死亡率的胎儿死亡，而雌二醇治疗野生型妊娠小鼠会造成胎儿的浪费。结果表明，在缺陷小鼠中，未能通过5α-还原雄激素导致其转化为雌激素，进而导致妊娠中期胎儿死亡。这些发现表明，雌性动物体内雄激素的5α-还原在预防妊娠期雌激素毒性中起着至关重要的作用。

BACKGROUND & AIMS: UNLABELLED:The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS:(1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS:(1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.

背景与目标： 未标记：本研究的目的是调查内源性阿片类药物是否参与垂体中内皮素-1的释放。为了验证这一假设，我们测量了在无水和缺水24小时的Wistar-Kyoto中阿片受体阻滞后，垂体中ET-1的血浆浓度以及垂体中免疫反应性ET-1（irET-1）的含量。大鼠。静脉注射安慰剂或纳曲酮（50微克/千克体重）。在两组中。收集躯干血液以确定血细胞比容，血浆钠和ET-1水平（RIA）。 ET-1在整个垂体中的免疫染色是通过胶体金标记进行的。使用计算机图像分析仪（MultiScan）在光学显微镜下对irET-1进行定量分析。
结果：（1）脱水24小时导致ET-1的外周血浓度明显升高。纳曲酮注射液在脱水和对照动物中均引起ET-1血浆浓度的显着升高。 （2）脱水大鼠垂体前叶和中间叶中irET-1的含量明显高于对照组。 （3）纳曲酮注射液导致脱水和对照动物的前叶，中叶和后叶内irET-1迅速大量降低。
结论：（1）脱水动物垂体中irET-1的升高和外周循环可能在维持水电解质平衡中起着重要作用。 （2）在正常和脱水动物中，μ阿片样物质系统似乎可以控制ET-1从垂体的释放。

BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.

背景与目标： ：我们在小鼠染色体6上构建了一个大于2-Mb区域的物理图，其中包含自然杀伤基因复合体（NKC）。该图包括14个重叠的酵母人工染色体的重叠群，我们在其上定位了25个NKC标记。 NKC遗传连锁基因编码> 17种蛋白质，这些蛋白质直接控制先天NK细胞介导的肿瘤溶解和疾病抵抗力。在本文中，我们显示Nkrp1基因聚集在A2m和Cd69基因侧翼的区域中，而大多数Ly49基因聚集在距离-1 Mb远的区域中。重要的是，保留了包含NKC的小鼠6号染色体和人类12p号染色体的同音间隔。 NKC物种保守性表明，人NKC可能含有小鼠病毒疾病抗性基因Cmv1和Rmp1的直向同源物。高分辨率的NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定，这些产物赋予NK细胞防御病毒病原体的能力。

BACKGROUND & AIMS: :Spherical pellets containing theophylline, calcium acetate and microcrystalline cellulose were extruded and spheronized, before being coated with six different pectins or alginates by interfacial complexation. The aim of this study was to discover the effect of the coatings on physico-mechanical properties that will be crucial in determining the pellets' utility as sustained release systems. An insoluble, smooth and uniformly thick coat of calcium polysaccharide was formed around the core pellets. A factorial experiment was designed to investigate the effect of pellet size and polysaccharide type and concentration on the entrapment efficiency, mechanical properties and other physical characteristics. Coated pellets were observed by scanning electron microscopy and, depending on the particular polysaccharide used, the dry coats were found to be 30-80 microm thick. The size of pellet, the type and concentration of polysaccharide influenced the yield of theophylline in the coated pellets. Although the mechanical properties of the pellets were improved by applying any of the gel coats, use of an alginate with a high content of guluronic acid or an amidated pectin coating gave the best results. This is probably because both of these have significant potential to form very stable cross-links within the gel coats.

背景与目标： ：将含有茶碱，乙酸钙和微晶纤维素的球形小球挤出并滚圆，然后通过界面络合用六种不同的果胶或藻酸盐包衣。这项研究的目的是发现包衣对物理机械性能的影响，这对于确定微丸作为缓释系统的用途至关重要。在核心药丸周围形成了不溶的，光滑且均匀厚的钙多糖涂层。设计了析因实验，以研究颗粒大小，多糖类型和浓度对包封效率，机械性能和其他物理特性的影响。通过扫描电子显微镜观察包衣的小丸，并且根据所使用的特定多糖，发现干衣的厚度为30-80微米。药丸的大小，多糖的类型和浓度影响了包衣药丸中茶碱的产量。尽管可通过使用任何凝胶包衣来改善丸粒的机械性能，但使用具有高含量古洛糖醛酸的藻酸盐或酰胺化果胶包衣的效果最佳。这可能是因为这两者都具有在凝胶涂层内形成非常稳定的交联的巨大潜力。

BACKGROUND & AIMS: :6-Pyruvoyltetrahydropterin synthase (PTPS) catalyzes the second step of tetrahydrobiopterin (BH4) synthesis. We previously identified PTPS orthologs (bPTPS-Is) in bacteria which do not produce BH4. In this study we disrupted the gene encoding bPTPS-I in Synechococcus sp. PCC 7942, which produces BH4-glucoside. The mutant was normal in BH4-glucoside production, demonstrating that bPTPS-I does not participate in BH4 synthesis in vivo and bringing us a new PTPS ortholog (bPTPS-II) of a bimodular polypeptide. The recombinant Synechococcus bPTPS-II was assayed in vitro to show PTPS activity higher than human enzyme. Further computational analysis revealed the presence of mono and bimodular bPTPS-II orthologs mostly in green sulfur bacteria and cyanobacteria, respectively, which are well known for BH4-glycoside production. In summary we found new bacterial PTPS orthologs, having either a single or dual domain structure and being responsible for BH4 synthesis in vivo, thereby disclosing all the bacterial PTPS homologs.

背景与目标： ：6-丙酮酰基四氢蝶呤合成酶（PTPS）催化四氢生物蝶呤（BH4）合成的第二步。我们先前在不产生BH4的细菌中鉴定了PTPS直系同源物（bPTPS-Is）。在这项研究中，我们破坏了Synechococcus sp。中编码bPTPS-1的基因。 PCC 7942，生产BH4-葡萄糖苷。该突变体在BH4-葡萄糖苷生产中是正常的，表明bPTPS-I不参与体内BH4合成，并为我们带来了双模块多肽的新PTPS直向同源物（bPTPS-II）。在体外对重组Synechocooccus bPTPS-II进行了分析，结果表明PTPS活性高于人的酶。进一步的计算分析表明，分别在绿色硫细菌和蓝细菌中分别存在单和双模块bPTPS-II直系同源物，这对于BH4-糖苷的生产是众所周知的。总之，我们发现了新的细菌PTPS直系同源物，具有单域或双域结构，并负责体内BH4的合成，从而揭示了所有细菌PTPS同源物。

BACKGROUND & AIMS: :The role of carbohydrate in the antigenic and immunogenic structure of bovine herpesvirus type 1 (BHV-1) glycoproteins gI and gIV was investigated. Deglycosylated proteins induced a significantly lower antibody response in rabbits than native glycoproteins suggesting that the immunogenicity of several epitopes on gI and gIV is carbohydrate-dependent. Loss of carbohydrate from gI also resulted in a significantly decreased ability to induce a serum neutralizing antibody response to BHV-1, due to modifications in three distinct carbohydrate-containing continuous epitopes. Similarly, in vitro lysis of BHV-1-infected cells was significantly reduced when antibodies raised against deglycosylated gI were employed; this was attributed to changes in two of the three carbohydrate-dependent neutralizing epitopes on gI. The oligosaccharides may be directly involved as actual components of these continuous epitopes, rather than in stabilization of the conformation of the protein. In contrast, carbohydrate removal from gIV did not have a significant effect on the capacity to stimulate a neutralizing antibody response. Accordingly, none of the neutralizing epitopes on gIV appeared to be carbohydrate-dependent. Similarly, lysis of virus-infected cells was not significantly reduced when antibodies specific for deglycosylated rather than native gIV were used. In contrast to the humoral response, the delayed-type hypersensitivity response was stronger in rabbits immunized with deglycosylated proteins than in those inoculated with native glycoproteins gI or gIV. Consequently, the carbohydrates on gI and gIV may play a dual role in the host's immune recognition and response by contributing to certain epitopes, but masking others. The implications for the development of a subunit vaccine against BHV-1 are discussed.

背景与目标： ：研究了碳水化合物在1型牛疱疹病毒（BHV-1）糖蛋白gI和gIV的抗原和免疫原性结构中的作用。与天然糖蛋白相比，去糖基化蛋白在兔中诱导的抗体应答显着降低，这表明gI和gIV上几个表位的免疫原性是碳水化合物依赖性的。由于三个不同的含碳水化合物的连续表位的修饰，gI中碳水化合物的损失还导致诱导针对BHV-1的血清中和抗体反应的能力大大降低。类似地，当使用针对去糖基化gI的抗体时，BHV-1感染细胞的体外裂解显着减少。这归因于gI上三个碳水化合物依赖性中和表位中两个的变化。寡糖可以直接作为这些连续表位的实际成分，而不是稳定蛋白质构象。相反，从gIV中去除碳水化合物对刺激中和抗体反应的能力没有显着影响。因此，gIV上的中和表位似乎都不是碳水化合物依赖性的。类似地，当使用对去糖基化而不是天然gIV具有特异性的抗体时，病毒感染细胞的裂解也没有明显减少。与体液反应相反，用去糖基化蛋白免疫的兔的迟发型超敏反应要强于用天然糖蛋白gI或gIV接种的兔。因此，gI和gIV上的碳水化合物可能通过贡献某些表位而掩盖其他表位，从而在宿主的免疫识别和反应中起双重作用。讨论了开发针对BHV-1的亚单位疫苗的意义。

BACKGROUND & AIMS: How an increase in blood pressure, in and of itself, induces hypertensive nephrosclerosis is unclear. In an earlier study we found that leukocyte infiltration, proximal tubular cell proliferation, matrix deposition and interstitial fibrosis occur in the unclipped kidney of 2 K 1 C Goldblatt hypertensive rats. In this study we tested the hypothesis that the cell surface adhesion molecule ICAM-1 is expressed on the vascular endothelium and tubular epithelium of unclipped kidneys at 4 weeks. As a positive control, we examined the clipped kidney as well. We found that systolic blood pressure was significantly elevated in renovascular hypertensive rats compared to sham-operated controls after 4 weeks (198 +/- 5 mmHg vs 121 +/- 2 mmHg, P < 0.001). Furthermore, quantitative (densitometry) measurements showed that ICAM-1 expression on vascular endothelium and on tubular cells was significantly increased in unclipped kidneys compared to controls (P < 0.05). The same was true for monocyte and granulocyte infiltration (P < 0.05). These same variables were even more prominent in the clipped kidneys, compared to unclipped and control kidneys (P < 0.05). Our data show that ICAM-1 is expressed in unclipped kidneys exposed to hypertension as well as in clipped kidneys exposed to ischemia. We suggest that mechanical injury induced by increased blood pressure is responsible for an inflammatory adhesion molecule-mediated response and concomitant renal injury.

背景与目标： 血压升高本身如何引起高血压性肾硬化尚不清楚。在较早的研究中，我们发现2 K 1 C Goldblatt高血压大鼠的未切除肾脏中发生白细胞浸润，近端肾小管细胞增殖，基质沉积和间质纤维化。在这项研究中，我们测试了以下假设：第4周，细胞表面粘附分子ICAM-1在未切除的肾脏的血管内皮和肾小管上皮细胞中表达。作为阳性对照，我们还检查了修剪的肾脏。我们发现，与假手术对照组相比，肾血管性高血压大鼠的收缩压在4周后显着升高（198 /-5 mmHg与121 /-2 mmHg，P <0.001）。此外，定量（密度测定）测量结果显示，与对照相比，未切除的肾脏在血管内皮和肾小管细胞上的ICAM-1表达显着增加（P <0.05）。单核细胞和粒细胞浸润也是如此（P <0.05）。与未修剪的和对照的肾脏相比，这些相同的变量在修剪的肾脏中甚至更为突出（P <0.05）。我们的数据表明，ICAM-1在暴露于高血压的未切除的肾脏以及暴露于缺血的切除的肾脏中表达。我们认为，血压升高引起的机械损伤是炎症粘附分子介导的反应和伴随的肾损伤的原因。

BACKGROUND & AIMS: :Thioredoxin-1 (TRX) is a small redox-active protein with antioxidative effects and redox-regulating functions. Cigarette smoking is a major etiological factor in the pathogenesis of a variety of diseases and recruits systemic immune and inflammatory responses. This report demonstrates that TRX attenuates the systemic inflammatory responses induced by cigarette smoking. The mRNA expressions of tumor necrosis factor alpha (TNF-alpha) and macrophage migration inhibitory factor (MIF) were suppressed in the spleen of TRX overexpressing transgenic mice (TRX-tg) exposed to cigarette smoking, compared with control C57BL/6 mice. In addition, protein carbonylation, a marker of cellular protein oxidation, was enhanced by cigarette smoking in the tissues of heart and liver in control mice more than in TRX-tg mice. These findings suggest that TRX may suppress the systemic inflammatory responses against cigarette smoking.

背景与目标： ：Thioredoxin-1（TRX）是一种小的氧化还原活性蛋白，具有抗氧化作用和氧化还原调节功能。吸烟是多种疾病发病机理中的主要病因，会招募全身免疫和炎症反应。该报告证明TRX减弱了吸烟引起的全身炎症反应。与对照C57BL / 6小鼠相比，暴露于吸烟的TRX过表达转基因小鼠（TRX-tg）的脾脏中肿瘤坏死因子α（TNF-α）和巨噬细胞迁移抑制因子（MIF）的mRNA表达受到抑制。另外，与TRX-tg小鼠相比，吸烟在对照小鼠的心脏和肝脏组织中增强了蛋白质羰基化作用，后者是细胞蛋白质氧化的标志。这些发现表明TRX可以抑制针对吸烟的全身性炎症反应。

BACKGROUND & AIMS: Poly(1-vinyl-2-pyrrolidinone) (PVP) and copolymers of 1-vinyl-2-pyrrolidinone are insoluble in water when crosslinked but they can absorb very large amounts of water to become syringe-injectable hydrogels. Such gels have been investigated recently as potential substitutes for the vitreous humour in the eye. In this study, during the cytotoxic evaluation by sulforhodamine B colorimetric assay of variously crosslinked PVP gels, it was found that many of them showed protective/growth promoting effects on 3T3 mouse fibroblasts in static cultures, a phenomenon encountered previously only with aqueous solutions of a limited number of natural or synthetic polymers. Particularly, the gels crosslinked with diethylene glycol dimethacrylate (DEGDMA) induced a significant enhancement of cell proliferation, especially in serum-free cultures. No correlation between this effect and the essential gel properties (chemical composition, viscoelasticity and equilibrium water content) could be established. The study demonstrated that crosslinked PVP hydrogels showed a serum-like growth promoting effect on an anchorage-dependent cell line, which may be due to physical protection, inability of the insoluble gels to penetrate cell membranes, and their ability to mimic the extracellular matrix.

背景与目标： 聚（1-乙烯基-2-吡咯烷酮）（PVP）和1-乙烯基-2-吡咯烷酮的共聚物在交联时不溶于水，但它们可以吸收大量的水，成为可注射注射器的水凝胶。最近已经研究了这种凝胶作为眼睛中玻璃体液的潜在替代物。在这项研究中，通过磺酰罗丹明B比色法对各种交联的PVP凝胶进行细胞毒性评估时，发现它们中的许多在静态培养物中对3T3小鼠成纤维细胞均显示出保护/促生长作用，这种现象以前仅在A的水溶液中会遇到。数量有限的天然或合成聚合物。特别是，用二甘醇二甲基丙烯酸二甲酯（DEGDMA）交联的凝胶可显着增强细胞增殖，特别是在无血清培养物中。在这种作用与基本的凝胶性质（化学组成，粘弹性和平衡水含量）之间没有相关性。该研究表明，交联的PVP水凝胶对锚定依赖性细胞系显示出类似血清的生长促进作用，这可能是由于物理保护，不溶性凝胶无法穿透细胞膜以及它们模仿细胞外基质的能力所致。