影响注意缺陷多动障碍患儿就诊因素的分析

目的分析探讨影响注意缺陷多动障碍（ADHD）患儿延迟就诊的因素。方法采用家庭环境量表（FES-CV）及自编简明就诊因素问卷对68例ADHD患儿的家长进行调查评定，分析影响延迟就诊的相关因素。结果61例患儿完成调查。所有因素经多元线性逐步回归分析，3个自变量差异具有统计学意义，分别为分型（Beta值：-0．449），接触知识（Beta值：0．369），父亲文化（Beta值：-0．268）。结论影响患儿就诊时间延迟的因素有3种情况，其顺序如下：（1）ADHD的注意缺陷型；（2）家长缺乏儿童心理卫重知识；（3）父亲的文化程度低。     

酞丁安对映体合成及其抗单纯疱疹病毒活性评价

酞丁安(3-酞酰亚胺-2-氧-正丁醛双缩氨硫脲,TDA)是药物研究所创制的抗病毒新药。为了研究其对映异构体(R),(S)-TDA对病毒活性及毒性是否有差异,并与消旋酞丁安(RS)-TDA的抗病毒活性及毒性进行比较,本文分别用已知构型的(R)-与(S)-丙氨酸为原料,通过缩合等6步反应,得到光学活性的(R)-,(S)-TDA,并与外消旋酞丁安比较其抗病毒活性及毒性。三者的抗单纯疱疹病毒活性与对细胞的毒性差别不大,说明消旋酞丁安临床使用是安全有效的。     

A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

A common FGFR3 mutation functions as a diagnostic marker for achondroplasia-group disorders in the Japanese population

Recent DNA studies performed by several groups have detected mutations of the gene encoding fibroblast growth factor receptor 3 (FGFR3) in patients with achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH), and thanatophoric dysplasia (TD). For this study, we analyzed theFGFR3 gene in 31 Japanese patients with typical ACH, four with HCH, three with a condition intermediate between ACH and HCH (ACH/HCH-intermediate), and one with TD. Of the 31 typical ACH patients, 29 showed a G1138 to A transition and the other two a G1138 to C transversion, both resulting in a common Gly380Arg substitution in the transmembrane domain of FGFR3. The one TD and the four HCH patients did not display any mutations in the transmembrane domain of FGFR3. Of the three ACH/HCH-intermediate cases, one patient showed the Gly380Arg substitution and one did not, and further analysis of the second patient revealed the presence of Asn540Lys substitution. The first patient was, therefore, genotypically diagnosed as ACH and the second as HCH. Peripheral blood leukocyte DNA analysis in the remaining ACH/HCH-intermediate patient indicated an unequal ratio of mutant to normal PCR products, possibly representing a somatic mosaic for the Gly380Arg mutation. Analysis of the common FGFR3 mutation thus appears to help in the molecular diagnosis of patients with achondroplasia-group disorders.     

胆囊收缩素－B受体拮抗剂的镇痛作用

用小鼠热水缩尾法研究了高选择性的ＣＣＫ－Ｂ受体拮抗剂ＰＤ１３４３０８的镇痛效应。ＰＤ１３４３０８在小鼠产生的镇痛有剂量依赖关系。阿片受体拮抗剂对抗其镇痛作用，表明阿片受体系统参与介导ＰＤ１３４３０８的镇痛。ＰＤ１３４３０８能加强吗啡的镇痛作用，但对α２受体激动剂可乐定的镇痛作用没有影响，表明ＣＣＫ－Ｂ受体拮抗剂对阿片受体系统作用有选择性。脑啡肽酶抑制剂ＳＣＨ３２６１５加强ＰＤ１３４３０８的镇痛作用，说明ＰＤ１３４３０８可能是通过增加内源性阿片物质产生镇痛作用的。另外，ＰＤ１３４３０８还参与吗啡镇痛耐受性的形成。     

Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines

Interleukin (IL)-4, IL-10, IL-13 and transforming growth factor beta (TGF-β) are known to regulate several monocyte functions, including inhibition of the synthesis of different cytokines. Using quantitative RT-PCR and flow cytometry analysis we investigated the effects of these cytokines on bacterial lipopolysaccharide (LPS)-induced tissue factor (TF) expression in human monocytes. The effects of IL-4 and IL-10 on monocyte chemoattractant protein-1 (MCP-1)- and C-reactive protein (CRP)-induced TF expression were also studied. A direct comparison revealed that IL-4, IL-10 and IL-13 all down-regulated LPS-induced TF expression in a concentration-dependent manner without the need for priming. In contrast, TGF-β required 4 h of priming to inhibit TF expression induced by LPS. IL-10 was the most powerful inhibitor, causing almost complete inhibition at 5 ng/ml. IL-4 and IL-13 exhibited a significantly lower inhibitory capacity even at concentrations of 100 ng/ml. IL-4 and IL-10 showed similar concentration-dependent inhibition of MCP-1- and CRP-induced TF expression. We also showed that the regulatory effect of the interleukins occurred at the mRNA level. In vivo , these inhibitory cytokines may play an important regulatory role in preventing thrombosis. IL-10, in particular, may be a possible candidate as a TF-preventing drug.     

神经生长因子治疗颅脑损伤52例

本文报告用水囊引产胎儿脑黑质制备的神经生长因子(NGF)治疗52例颅脑损伤的临床观察结果:显效率91%。有效率100%,轻、中型患者疗效明显,显效率100%。其中头昏头痛,语言障碍,精神异常,大小便失禁,肢体功能障碍都有明显疗效。而且对儿童和病程短者效果更佳。认为治疗机理可能是 NGF 能预防神经元坏死,促进神经元及其纤维增生有关。结果表明,NGF 在治疗脑外伤及其后遗症中疗效确切,在颅外伤及其后遗症中可广为应用。     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.