BACKGROUND & AIMS: We studied changes in glutamate receptors, expression of immediate early genes, and AP-1 DNA binding activity in the brains of phenobarbital (PB)-dependent and -withdrawn rats to investigate the possible involvement of activation of glutamate receptors in PB withdrawal syndrome. PB-dependent rats were prepared by feeding drug-admixed food for 5 weeks. Autoradiographic analysis showed that binding of [3H(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imin e (MK-801), an antagonist of N-methyl-D-aspartic acid (NMDA) receptors, increased significantly in the cerebral cortices of PB-dependent and 24-h-withdrawn rats. However, [3H]MK-801 binding in the hippocampus and [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and [3H]kainic acid binding in the hippocampus and cerebral cortex were essentially unchanged in both groups. PB withdrawal seizures were followed by increased expression of c-fos mRNA in the hippocampus and cerebral cortex and of c-jun mRNA in the cerebral cortex. The induction of c-fos and c-jun mRNA was suppressed by administration of MK-801. Furthermore, PB withdrawal enhanced AP-1 DNA binding activity in the brain. The present findings suggest functional enhancement of glutamatergic neurotransmission during the development of PB withdrawal syndrome.

背景与目标： 我们研究了苯巴比妥 (PB) 依赖性和退缩大鼠大脑中谷氨酸受体的变化，即刻早期基因的表达以及AP-1的DNA结合活性，以研究谷氨酸受体激活在PB戒断综合征中的可能参与。通过喂养混合药物的食物5周制备PB依赖性大鼠。放射自显影分析显示，N-甲基-d-天冬氨酸 (NMDA) 受体拮抗剂 [3H(+)-5-甲基-10,11-二氢-5H-二苯并 [a，D] cyclohepten-5，10-敏e (MK-801) 的结合，PB依赖性和24h撤回大鼠的大脑皮层显着增加。然而，[3h] MK-801在海马和 [3H]6-氰基-7-硝基喹喔啉-2结合，海马和大脑皮层中的3-二酮 (CNQX) 和 [3H] 海藻酸结合在两组中基本上没有变化。铅戒断发作后，海马和大脑皮层中c-fos mRNA的表达增加，大脑皮层中c-6月mRNA的表达增加。诱导c-MK-801可抑制fos和c-6月mRNA。此外，铅戒断增强了大脑中的AP-1 DNA结合活性。目前的发现表明，在铅戒断综合征的发展过程中，谷氨酸能神经传递的功能增强。

BACKGROUND & AIMS: The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

背景与目标： Dlx同源盒基因家族在胚胎颅面外胚层和外胚间质中以复杂的模式表达。先前的研究表明，Dlx-2对于鼠第一和第二鳃弓近端区域的发育至关重要。在这里，我们描述了具有Dlx-1和-2突变的小鼠的颅面表型。对具有Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了额外的证据，表明Dlx基因调节鳃弓的近端模式。此分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特和重叠作用。此外，缺少Dlx-1和-2的小鼠具有独特的异常，包括缺少上颌磨牙。Dlx-1和-2在近侧和远侧第一和第二拱形中表达，但只有近侧区域是异常的。Dlx-1、-2、-3、-5和-6的嵌套表达模式为预测每个基因的区域特异性需求的模型提供了证据。最后，Dlx-2和Dlx-1和-2突变体具有异位的头骨成分，类似于在系统发育上更原始的脊椎动物中发现的骨骼和软骨。

BACKGROUND & AIMS: Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

背景与目标： Interleukin-1beta (IL-1beta) 与肝脏疾病密切相关。IL-1beta在血管平滑肌细胞中产生一氧化氮 (NO)，并通过环鸟苷3 '，5'-单磷酸 (cGMP) 松弛血管平滑肌。在这项研究中，我们评估了IL-1beta对培养的Ito细胞的松弛作用。从雄性Wistar大鼠的肝脏中分离Ito细胞，并培养24小时。使用共聚焦激光显微镜检查诱导型一氧化氮合酶 (iNOS) 和cGMP的免疫定位以及cGMP的荧光强度。Ito细胞用0、200和1,000 pmol/L IL-1beta处理，12小时后测定细胞内cGMP浓度。此外，在12小时内观察到用200和1,000 pmol/L IL-1beta处理和不用IL-1beta处理的Ito细胞，并比较在添加IL-1beta前后相同Ito细胞的面积。接下来，通过IL-1beta处理检查了N(G)-单甲基-L-精氨酸 (L-NMMA) 和S-亚硝基-N-乙酰基-DL-青霉胺 (SNAP) 对Ito细胞松弛的影响。在Ito细胞中，观察到iNOS的免疫荧光，加入IL-1beta后cGMP的荧光强度增加。加入IL-1beta后，细胞内cGMP浓度呈剂量依赖性增加。与未处理组相比，IL-1beta-treated组的细胞面积显着增加。IL-1beta处理对Ito细胞的松弛以剂量依赖性方式被l-nmma抑制，但被SNAP增强。这些结果表明，IL-1beta在培养的Ito细胞中产生NO，并通过cGMP使细胞松弛。

BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

背景与目标： 我们报告了一项西班牙人群中GABR beta1基因的四核苷酸重复多态性与躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者，因为已经在患者中描述了严重的GABergic改变。尽管我们的结果并未揭示出躁狂抑郁症与GABR beta1之间存在关联的明确证据，但我们发现女性亚群的患者与对照组之间存在显着差异。

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，它们的表达可以通过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，这些顺式作用调节基序之一是核因子X2 (NF-X2) 结合的X2-box。在这里，我们介绍了编码NF-X2的全长cDNA克隆隔离和表征。通过表达cDNA克隆分离该cDNA克隆，并编码人c 6月蛋白，该蛋白与c-Fos一起形成异二聚体激活蛋白1转录复合物。尽管b细胞中不存在c-Fos/c-6月异二聚体，但它们在II类非表达细胞中形成并结合X2-box。因此，c-Fos/c-6月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：

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： : 已从苦瓜的种子和果实中分离并纯化出一种新的人类免疫缺陷病毒 (HIV) 抑制剂，使之同质。该化合物MAP 30 (苦味子抗HIV蛋白) 是约30 kDa的碱性蛋白。它表现出对无细胞HIV-1感染和复制的剂量依赖性抑制，通过以下方式测量 :( i) 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; 和 (iii) HIV-1感染的H9细胞中的病毒相关逆转录酶 (RT) 活性。在这些测定中50% 抑制所需的剂量 (ID50) 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 5月30日是治疗HIV-1感染的有用治疗剂。已确定MAP 30的N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：

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：

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，被认为负责产生针对菠萝蛋白酶处理的自体红细胞 (br-rbc) 的天然自身抗体。这里显示大量的常规CD5-negative脾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细胞群体产生的。然而，体内用细菌脂多糖刺激优先激活CD5 b细胞组，使其分泌抗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： : 缺乏类固醇5α-还原酶1型的雌性小鼠的产仔数减少。纯合缺陷雌性的平均产仔为2.7幼仔，而野生型对照为8.0幼仔。在突变动物中，卵子发生，受精，植入和胎盘形态似乎正常。胎儿损失发生在妊娠10.75和11.0之间，与妊娠中期胎盘雄激素产生激增和野生型小鼠蜕膜中5α-还原酶1型表达的诱导相称。在妊娠第9天，雄烯二酮和睾丸激素的血浆水平高2至3倍，在整个妊娠早期和中期，敲除小鼠的雌二醇水平长期升高2至3倍。施用雌激素受体拮抗剂或芳香化酶抑制剂可逆转突变小鼠的高胎儿死亡率，而雌二醇处理野生型妊娠小鼠会导致胎儿浪费。结果表明，在缺陷小鼠中，未能减少5α-雄激素会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，雌性动物中雄激素的5α 减少在预防怀孕期间的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：

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，醋酸钙和微晶纤维素的球形颗粒挤出并球形化，然后通过界面络合用六种不同的果胶或藻酸盐包被。这项研究的目的是发现涂层对物理机械性能的影响，这对于确定颗粒作为持续释放系统的效用至关重要。在核心颗粒周围形成不溶性，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到包被的颗粒，根据所用的特定多糖，发现干涂层的厚度为30-80微米。颗粒的大小，多糖的类型和浓度影响包衣颗粒中茶碱的产量。尽管通过施加任何凝胶涂层可以改善颗粒的机械性能，但使用具有高含量古罗糖醛酸的藻酸盐或酰胺化的果胶涂层可提供最佳结果。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: :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牛疱疹病毒1型 (BHV-1) 糖蛋白gI和gIV的抗原性和免疫原性结构中的作用。与天然糖蛋白相比，去糖基化蛋白诱导的兔抗体反应明显降低，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血清中和抗体对BHV-1的反应的能力显着降低。同样，当使用抗去糖基化gI的抗体时，BHV-1-infected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的两个的变化。寡糖可能直接作为这些连续表位的实际成分参与，而不是稳定蛋白质的构象。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。同样，当使用对去糖基化而非天然gIV具有特异性的抗体时，病毒细胞的裂解也没有显着减少。与体液反应相反，用去糖基化蛋白免疫的兔子的迟发型超敏反应比用天然糖蛋白gI或gIV接种的兔子更强。因此，gI和gIV上的碳水化合物可能通过促进某些表位而在宿主的免疫识别和反应中起双重作用，但掩盖了其他表位。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： 目前尚不清楚血压本身的升高如何引起高血压肾硬化。在较早的研究中，我们发现2 K 1 C Goldblatt高血压大鼠的未夹肾中发生白细胞浸润，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: 细胞表面粘附分子ICAM-1在4周时在未夹住的肾脏的血管内皮和肾小管上皮上表达。作为阳性对照，我们也检查了截断的肾脏。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 vs 121/- 2 mmHg，P <0.001)。此外，定量 (密度测定法) 测量显示，与对照组相比，未夹住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)。与未夹肾和对照肾相比，这些相同的变量在夹肾中更为突出 (P <0.05)。我们的数据显示，ICAM-1在暴露于高血压的未夹肾以及暴露于缺血的夹肾中表达。我们建议由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。