两种不同固位结构附着体义齿修复游离端缺失基牙及缺牙区牙槽嵴应力分布的比较

目的探讨不同固位结构的附着体义齿应力分布特点,为临床应用附着体义齿种类的选择提供依据。方法应用三维有限元的方法分别测定并比较应用键槽缓冲式附着体和柱状附着体修复下颌单侧游离端缺失基牙及牙槽嵴应力分布情况。结果键槽缓冲式附着体义齿对基牙产生应力值小于柱状附着体义齿,对缺牙区牙槽嵴应力大于柱状附着体义齿。结论键槽缓冲式附着体义齿较适合于基牙条件差的义齿修复,柱状附着体义齿较适合于缺牙区牙槽嵴条件差的义齿修复。     

Mechanism of action of doxepin in the treatment of chronic urticaria

The present study examined 15 patients previously resistant to conventional antihistamines, in which doxepin at doses in the range of 50-75 mg/day was shown to be effective in treatment of chronic urticaria and without significant adverse side effects. However, some controversy remains about its mechanism of action in this particular disease. The aim of the present study was to examine the muscarinic, H1 and H2 blocking activity of doxepin. The following methods were used: a) gastric acid hypersecretion induced by histamine and carbachol in the pylorus-ligated rat preparation; b) contractile dose-response curves to histamine and carbachol in the guinea pig ileum; c) dimaprit-stimulated guinea pig atrium in vitro. pA2 values were determined for atropine, mepyramine, cimetidine and doxepin. As regards histamine, doxepin (50 mg/kg, po) increased gastric pH and decreased secretion volume, gastric acid concentration and total acid output; with carbachol, doxepin weakly antagonized those values. In the ileum, doxepin competitively antagonized carbachol (pA2 = 7.08) and histamine (pA2 = 9.72); pA2 values for atropine and mepyramine against carbachol and histamine were 9.11 and 8.82, respectively. In the atria, the dose-response curve to dimaprit was also competitively displaced by cimetidine (pA2 = 6.69) and doxepin (pA2 = 6.00). Doxepin displayed a very high affinity for H1 histamine receptor, being 8-fold more potent than mepyramine. Doxepin showed significant H2 blocking activity which was 5 times less potent than that of cimetidine. Doxepin competitively antagonized carbachol in the guinea pig ileum, and was 107 times less potent than atropine. The combined H1, H2 and muscarinic blocking activities of doxepin may contribute towards explaining its clinical efficacy in the treatment of chronic urticaria.     

A study of confidential unit exclusion

The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse.     

Adaptive differentiation of murine lymphocytes. IV. (Responder × Nonresponder) F(1) T cells can be taught to preferentially help nonresponder,rather than responder, B cells

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder × nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.     

Deregulation of NMDA-receptor function and down-stream signaling in APP[V717I] transgenic mice

Evidence is accumulating for a role for amyloid peptides in impaired synaptic plasticity and cognition, while the underlying mechanisms remain unclear. We here analyzed the effects of amyloid peptides on NMDA-receptor function in vitro and in vivo. A synthetic amyloid peptide preparation containing monomeric and oligomeric A beta (1-42) peptides was used and demonstrated to bind to synapses expressing NMDA-receptors in cultured hippocampal and cortical neurons. Pre-incubation of primary neuronal cultures with A beta peptides significantly inhibited NMDA-receptor function, albeit not by a direct pharmacological inhibition of NMDA-receptors, since acute application of A beta peptides did not change NMDA-receptor currents in autaptic hippocampal cultures nor in xenopus oocytes expressing recombinant NMDA-receptors. Pre-incubation of primary neuronal cultures with A beta peptides however decreased NR2B-immunoreactive synaptic spines and surface expression of NR2B containing NMDA-receptors. Furthermore, we extended these findings for the first time in vivo, demonstrating decreased concentrations of NMDA-receptor subunit NR2B and PSD-95 as well as activated alpha-CaMKII in postsynaptic density preparations of APP[V717I] transgenic mice. This was associated with impaired NMDA-dependent LTP and decreased NMDA- and AMPA-receptor currents in hippocampal CA1 region in APP[V717I] transgenic mice. In addition, induction of c-Fos following cued and contextual fear conditioning was significantly impaired in the basolateral amygdala and hippocampus of APP[V717I] transgenic mice. Our data demonstrate defects in NMDA-receptor function and learning dependent signaling cascades in vivo in APP[V717I] transgenic mice and point to decreased surface expression of NMDA-receptors as a mechanism involved in early synaptic defects in APP[V717I] transgenic mice in vivo.     

在白色念珠菌URM3622中生产胶原酶

采用三种设计方案考察了白色念珠菌URM3622胞外分泌生产胶原酶的培养条件。首先进行26—2部分因子试验,结果表明转速和底物浓度对胶原酶的产量影响显著。根据以上结果,又设计了两次连续的23全因子分析,结果表明,在pH7．0、转速160r／min、底物浓度2％条件下培养白色念珠菌,发酵所得胶原酶活性最高。在pH8．2、45℃的环境中,胶原酶活性最大。所获胶原酶在pH7．2～8．2及28～45℃范围内稳定。     

OSAHS患者血清8-isoPG、LTB4、TNF-α、IL-10和Hs—CRP检测的临床意义

目的 探讨OSAHS患者血清炎症因子检测的临床意义.方法 OSAHS患者40例和正常对照30例,采用酶联免疫技术检测血清8-异前列烷(8-isoPG)、白三烯B4(LTB4)、TNF-α、IL-10水平,以全自动生化分析仪测定高敏C反应蛋白(Hs-CRP)的浓度,并与睡眠监测指标进行相关性分析.其中20例OSAHS患者分别经自动持续气道正压通气(Auto-CPAP)或悬雍垂软腭咽成形术(UPPP)治疗3个月后,复查睡眠呼吸监测和上述炎症因子.结果 ①OSAHS组睡眠后血清中8-isoPG、LTB4、TNF-α、IL-10和Hs-CRP分别为(36.59±14.89)ns/L、(14.75±6.25)μg/L、(1022.13±97.57)ns/L、(4.68±3.42)ng/L和(2.46±1.58)mg/L,正常对照组分别为(19.91±7.76)ng/L、(1.43±0.72)μg/L、(540.00±78.70)ng/L、(7.41±4.49)ng/L和(0.30±0.16)mg/L,两组比较差异均有统计学意义(P均<0.01).②OSAHS组血清中8-isoPG、LTB4、TNF-α 和Hs-CRP随病情严重度增高而升高,IL-10随病情严重度增高而降低(P均<0.05).③OSAHS患者睡眠后血清中8-isoPG、LTB4、TNF-α、Hs-CRP与呼吸暂停低通气指数(AHI)呈正相关(r值分别为0.863,0.746,0.868和0.842,P均<0.01);与睡眠中最低血氧饱和度(LspO2)呈负相关(r值分别为-0.623,-0.524,-0.618和-0.562,P均<0.01);与平均血氧饱和度(MSpO2)呈负相关(r值分别为-0.654,-0.573,-0.537和-0.589,P均<0.01);OSAHS患者睡眠后血清中IL-10与AHI呈负相关(r=-0.722,P<0.01),与睡眠中LSpO2呈正相关(r=0.564,P<0.01),与MSpO2呈正相关(r=0.505,P<0.01).@20例OSAHS患者经治疗3个月后血清8-isoPG、LTB4、TN-α及Hs-CRP均较治疗前下降,血清中IL-10比治疗前上升(P<0.01).⑤OSAHS患者治疗后血清8-isoPG、IL-10与正常对照组比较无显著差异(P0.05),血清LTB4、TNF-α和Hs-CRP比正常对照组水平高(P<0.01).结论 OSAHS患者存在夜间低氧后炎症反应及氧化应激增强,抗炎因子水平降低.炎症因子检测结合睡眠呼吸监测对判断OSAHS严重程度和治疗效果具有一定的临床意义.     

Pancreatic duct cells in human islet cell preparations are a source of angiogenic cytokines interleukin-8 and vascular endothelial growth factor

OBJECTIVE—Engraftment and function of human islet cell implants is considered to be dependent on their rapid and adequate revascularization. Studies with rodent islet grafts have shown that vascular endothelial growth factor (VEGF) expression by β-cells can promote this process. The present work examines whether human islet preparations produce VEGF as well as interleukin (IL)-8, another angiogenic protein, and assesses the role of contaminating duct cells in VEGF and IL-8–mediated angiogenesis.RESEARCH DESIGN AND METHODS—Human islet and pancreatic duct cell preparations are compared for their respective expression and production of VEGF and IL-8 during culture as well as following transplantation in nonobese diabetic (NOD)/scid mice. The associated angiogenic effects are measured in an in vitro aortic ring assay and in an in vivo chick embryo chorioallantoic membrane assay.RESULTS—Cultured pancreatic duct cells expressed 3- and 10-fold more VEGF and IL-8, respectively, than cultured human islet endocrine cells and released both proteins at angiogenic levels. The angiogenic effect of purified duct cells was higher than that of purified endocrine islet cells and was completely blocked by a combination of IL-8 and VEGF antibodies. Human duct cell implants under the kidney capsule of NOD/scid mice expressed higher levels of IL-8 and VEGF than human islet cell implants and induced circulating IL-8 and VEGF levels during the first day posttransplantation.CONCLUSIONS—Human duct cell–released IL-8 and VEGF may help revascularization of currently used human islet cell grafts. Further work should examine whether and when this effect can prevail over other inflammatory and immune influences of this cell type.Islet cell transplant protocols have been designed to restore type 1 diabetes in patients, but the function of the implants was found to progressively decrease, leading to <15% insulin-independent recipients after 5 years (1). Several variables can explain this loss in metabolic efficacy. We have observed that the functional β-cell mass in insulin-independent recipients at posttransplant month 12 is only 20–30% of that in normal control subjects (2). It is so far unknown to which extent this quantitative deficit results from an insufficient mass before injection, from poor engraftment, and/or from destruction by inflammation and immune reaction during the first year. There is evidence that β-cell loss is considerable during the first days posttransplantation (3), which has intensified attention to the process of revascularization in the islet cell implant (4,5).In their normal pancreatic habitat, islet cells are embedded in a dense microvascular network that should meet the high oxygen and nutrient needs of the endocrine cells. The islet isolation process and the subsequent in vitro steps, however, disrupt capillary structures and their association with endocrine cells, making the formation of new vessels necessary for adequate graft survival. In rodent models, the islet blood flow appears restored within 1–2 weeks after transplantation (5); during the first posttransplant week, transplanted cells seem thus dependent on adequate diffusion of oxygen and nutrients, while mechanisms should be initiated to start sprouting of vessels into their intrahepatic sites. New-vessel formation can be induced and directed by factors released by the tissue to be irrigated (6). Islet β-cells are known to produce vascular endothelial growth factor (VEGF), and several studies have been reported on the beneficial effects of an increased VEGF expression or availability on survival of transplanted islets in rodents (7). However, it remains unclear to which extent VEGF release from normal β-cells succeeds in rapidly inducing an adequate blood supply to the implants. Moreover, such angiogenic action might be less pronounced in human islet cell preparations, since they contain much lower percentages of β-cells than isolated rodent islets (8). Our transplant protocols are conducted with cultured human islet cell grafts in which duct cells represent the main contaminant, often reaching percentages that approximate the percent of β-cells (2,8). To assess the possible role of duct cells in human islet cell implants, we have purified these cells from human donor organs and examined their properties in vitro as well as following transplantation in immune-deficient mice (9,10). It was thus found that human pancreatic duct cells react much more vigorously to cytokines than the islet endocrine cells when comparing cellular major histocompatibility complex II expression, induction of nitric oxide (NO) synthase followed by production of NO, and synthesis and subsequent release of the inflammatory cytokine tumor necrosis factor (TNF)-α (11–13). In addition, duct cells were shown to express CD40 that rapidly activated nuclear factor-κB upon ligation, lending further support to the view that duct cells may actively contribute to the inflammatory process leading to diabetes and/or to islet graft rejection (9,14). During these in vitro studies on human duct cells, we noticed that they could produce several cytokines, among which interleukin (IL)-8 (CXCL8) appeared more abundant. IL-8 is known as a potent inducer of angiogenesis (15,16), involving effects on chemotaxis, survival, and proliferation of tissue-specific endothelial cells through interaction with its cognate G protein–coupled receptors CXCR1 and CXCR2 (17,18). We therefore compared the production of IL-8 and VEGF by cultured human pancreatic duct cells and islet cell preparations and examined whether these duct cell products exhibit angiogenic properties in laboratory models.     

儿童癌症幸存者成年后的慢性疾病

由于治疗方法的进步,近80%的儿童和青少年癌症患者能够长期生存。在美国,约有270000例儿童癌症的幸存者,即每640名20至39岁成年人中就有一名幸存者。大量的幸存者有利于儿童癌症治疗后长期健康结果的研究。现在可以明确的是,化疗和放疗所致的儿童各器官系统损害在临床上可能潜伏多年。为了全面了解治疗儿童癌症而继发的健康问题,重要的是衡量三项长期结果:健康状况、死亡率和患病率。这三项中,关于前两项已有相当好的研究报道。在一项对20227例癌症5年生存者的回顾性分析中,Mertens等发现以下原因导致的超额死亡率具有统计学意义:继发癌症(…