Comparison of glucuronidating activity of two human cDNAs, UDPGTh1 and UDPGTh2

Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 and UDPGTh2 were previously shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (e.g., estriol and 3,4-catechol estrogens), respectively. In this study we have found that the UDPGTh-2-encoded isoform (UDPGTh2) and HLUG25-encoded isoform (UDPGTh1) have parallel aglycone specificities. When expressed in COS 1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol, 17-epiestriol, and HDCA, but the UDPGTh2 isozyme was 100-fold more efficient than UDPGTh1. UDPGTh1 and UDPGTh2 were 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which conferred the substrate specificity. The data indicated that a high level of conservation in the amino terminus was not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh1/UDPGTh2 chimeric cDNA constructed at their common restriction sites,Sac 1 (codon 297),Nco 1 (codon 385), andHha 1 (codon 469), showed that nine amino acids between residues 385 and 469 were important for catalytic efficiency, suggesting that this region represented a domain which was critical for the catalysis but distinct from that responsible for aglycone selection. These data indicate, that UDPGTh2 is a primary isoform responsible for the detoxification of the bile salt intermediate as well as the active estrogen intermediates.     

Topical anti-inflammatory activity of dianemycin isolated fromStreptomyces sp. MT 2705-4

In order to develop new anti-inflammatory agents having different action mechanisms compared with nonsteroidal and steroidal anti-inflammatory drugs, the culture broths of various actinomycetes isolated from soil were screened using anin vivo mouse ear edma assay and one strain (Streptomyces sp. MT 2705-4: KCTC 8651P) was selected. Activity-guided purification led to the isolation of a polyether compound, dianemycin. Topically, dianemycin showed a potent anti-inflammatory activity in mouse ear edema induced by croton-oil or arachidonic acid. ED(50) value of dianemycin was found to be 0.8 mg/ear compared to 0.4 mg/ear of prednisolone in croton-oil ear edema. However, dianemycin did not show the inhibitory activity in UV-erythema and delayed hypersensitivity reaction. These results indicate that dianemycin is a potential topical anti-inflammatory agent.     

Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus at a teaching hospital in Taiwan

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981-1994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teaching hospital in Taiwan. The number of nosocomial MRSA infections increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2 episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The most common infection site was surgical wounds, which accounted for 26.3% of total 577 episodes of nosocomial MRSA infections during the study period. However, bacteraemia has become more and more common during the past 14 years. MRSA infections occured more frequently in patients stayed in the burn unit and other intensive care units than in the general wards. Other than oxacillin, the resistance rate to many other antibiotics also increased in S. aureus strains causing nosocomial infections in this hospital. Vancomycin remained active to all these S. aureus strains, even until 1994.     

Presence of apolipoprotein E on extracellular neurofibrillary tangles and on meningeal blood vessels precedes the Alzheimer β-amyloid deposition

The localization of apolipoprotein E (ApoE) has been examined immunohistochemically in the autopsied brains of middle-aged and old-aged control subjects, with and without amyloid protein (A) deposits, and of Alzheimer's disease patients. Senile plaques were consistently labeled with ApoE antiserum even in the very early stage of senile plaque formation seen in the fifth decade. In the cerebellar molecular layer, small dots of ApoE immunoreactivity, which were prominent in the Alzheimer's disease subjects, were observed in addition to immunoreactivity in diffuse plaques. ApoE antisera labeled all of the extracellular neurofibrillary tangles (NFT), whereas only a small minority of extracellular NFT were positive for A. A punctate pattern of ApoE immunoreactivity was seen at the media of the meningeal vessels lacking amyloid, when senile plaques were present in the nearby cortex. In the early stage of amyloid angiopathy, the distribution of ApoE immunoreactivity was much more extensive than that of A positivity. These findings suggest that ApoE accumulates in the early stage of senile plaque formation and, furthermore, that ApoE accumulation precedes A deposition in extracellular NFT and amyloid angiopathy.     

Solute Absorption from the Airways of the Isolated Rat Lung. IV. Mechanisms of Absorption of Fluorophore-Labeled Poly-α,β-[N(2-Hydroxyethyl)-DL-Aspartamide]

The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-,-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (M _wand M _n, respectively) using high-performance gel-permeation chromatography. Values for M _w and M _n were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V _max, of approximately 180 µg or 0.027 µmol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer.     

Evaluation of a novel bis-naphthalimide anticancer agent,DMP 840, against human xenografts derived from adult,juvenile, and pediatric cancers

The new bis-naphthalimide antitumor agent (R,R)2,2-[1,2-ethanediylbis[imino(1-methyl-2.1-ethanediyl)]-bis {5-nitro-1H-benz[de]-isoquinoline-1,3-2H) dione} dimethanesulfonate (DMP 840) was evaluated against parental and multidrug-resistant human KB cell lines in vitro and against these lines growing as xenografts in immunedeprived mice. In vitro, KB8-5 cells were 50-fold resistant to vincristine but only 16-fold resistant to DMP 840 as measured by clonogenic survival. For in vivo evaluation, DMP 840 was given by i. v. injection daily for 9 days or for 5 days/week for 2 consecutive weeks [(dx5)2]. In contrast to the cross-resistance of KB cell lines in vitro, both KB3-1 and KB8-5 tumors were highly and equally sensitive to DMP 840; only KB3-1 xenografts demonstrated sensitivity to vincristine, which was consistent with the in vitro results. DMP 840 was also evaluated against a panel of human tumors comprising colon adenocarcinoma and rhabdomyosarcoma xenografts. Against eight lines of colon adenocarcinoma, DMP 840 caused a high frequency of partial and complete regressions in two lines and significant inhibition of growth in two lines. DMP 840 caused complete regressions in five of six lines of advanced rhabomyosarcomas, demonstrating a broad range of effective dose levels. The pattern of activity against this tumor panel was similar but not identical to that of two inhibitors of topoisomerase I. There was no cross-resistance to DMP 840 in xenografts selected for resistance to vincristine or in a rhabdomyosarcoma selected for resistance to the topoisomerase I inhibitor topotecan. In contrast, a colon tumor selected for topotecan resistance was completely resistant to DMP 840. Slight cross-resistance to DMP 840 was demonstrated in a rhabdomyosarcoma xenograft that was selected for primary resistance to melphalan and was cross-resistant to topoisomerase I inhibitors. The pattern of activity and cross-resistance in these tumors was compared with that shown by two agents that inhibit topoisomerase I: topotecan and CPT-11.This work was supported in part by CA23099, Cancer Center Support (CORE) grant CA21675, The Du Pont Merck Pharmaceutical Company, and by American Lebanese Syrian Associated Charities (ALSAC)     

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

ＳＥＡＲＣＨＦＯＲＨＥＲＰＥＳＳＩＭＰＬＥＸＶＩＲＵＳＴＹＰＥ２（ＨＳＶ－２）ＡＮＤＨＵＭＡＮＰＡＰＩＬＬＯＭＡＶＩＲＵＳ（ＨＰＶ）ＩＮＴＨＥＮＯＲＭＡＬＡＮＤＡＢＮＯＲＭＡＬＣＥＲＶＩＣＡＬＳＡＭＰＬＥＳＺｈａｎｇＷｅｉ;张伟;ＪｉｎＳｈｕｎｑｉａ...     

106例肺切除术分析

1982年3月～1994年12月,我们为各类肺部疾病进行肺切除术106例。术中、术后发生并发症23例次占21．6％,术后30日内死亡2例占1．8％．文内着重对支气管胸膜瘘、血胸、肺血管损伤大出血、癌栓脱入对侧肺支气管、肺静脉癌栓脱入股动脉及心跳聚停等并发症的防治及紧急处理进行了讨论。此外,作者认为,肺叶切除术目前在大多数病例仍是肺癌外科的“标准术式”,但在心肺功能允许并由于技术或肿瘤学原因非行全肺切除术才能达到根治性切除时,就要果断地行全肺切除,心包外处理肺血管有困难时,要毫不迟疑地采取心包内途径。     

上海市50岁及以上人群维生素D水平与握力的关联研究

目的 探讨上海市≥50岁人群维生素D水平与握力的关系。方法 数据来源于WHO全球老龄化与成人健康研究我国上海市2018-2019年数据,采用logistic回归模型分析维生素D水平与握力的关系,进一步按照性别、年龄及乳制品摄入情况进行分层;采用限制性立方样条曲线绘制维生素D水平与低握力的剂量-反应曲线。结果 共4 391人纳入研究,其中男性2 054人（46.8%）;年龄（67.02±8.81）岁;低握力1 421人（32.4%）;维生素D不足及缺乏分别为1 533人（34.9%）和401人（9.1%）。在调整相关混杂因素后,logistic回归分析结果显示,维生素D缺乏的人群发生低握力的风险更高（OR=1.41,95%CI：1.09~1.83）;在男性中,调整相关混杂因素后,维生素D缺乏与低握力发生风险呈显著正相关（OR=1.67,95%CI：1.12~2.50）,而女性中两者之间无关联（OR=1.30,95%CI：0.97~1.74）;在60~69岁及≥80岁年龄组中,调整相关混杂因素后,维生素D缺乏与低握力发生风险呈显著正相关（OR=1.57,95%CI：1.05~2.35;OR=2.40,95%CI：1.08~5.31）,在乳制品摄入<250 ml/d的人群中,调整相关混杂因素后,二者之间呈显著正相关（OR=1.57,95%CI：1.17~2.09）,而在乳制品摄入≥250 ml/d的人群中无明显关联。限制性立方条样图显示,低握力的发生风险可能随维生素D含量的上升而降低,但差异无统计学意义（P>0.05）。结论 维生素D水平与握力存在一定的关系,维生素D缺乏人群出现低握力的风险更高。     

口腔修复中高熔铸件浇铸不全的原因浅析及预防

目的:探讨高熔铸件浇铸不全的可能原因。方法:通过对临床85件可摘铸件缺损的初浅分析,总结出浇铸不全的可能原因。结果:高熔铸件浇铸不全的原因有以下7个方面:①铸金量不足;②熔金温度过低;③离心力不够;④铸道布局不当;⑤铸件过薄;⑥高温包埋料透气性差;⑦铸圈温度下降。结论:通过查找原因,总结出预防的方法,对提高高熔铸件修复体的质量有一定的作用。