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Extracellular purines and their receptors in immunoregulation. Review of recent advances. 细胞外嘌呤及其受体在免疫调节中的作用。回顾最近的进展。
Pub Date : 1998-10-01 DOI: 10.1272/jnms1923.65.351
M V Sitkovsky

T cells are important effector cells in natural antiviral and anticancer immunity. It is important to reveal the cellular and molecular requirements for T cell differentiation and effector functions. We explored the idea that the final outcome of antigen receptor-driven immune processes is at least partially determined by physiologically abundant small signaling molecules in extracellular environment of lymphocytes in different tissues. Extracellular purines (ATP and adenosine) and their (purinergic) receptors were studied as an example of such molecules. Studies of functional effects of extracellular ATP and adenosine in immunoregulation have evolved in studies of individual molecules of purinergic receptors and of phosphorylation of extracellular domains of functionally important proteins. ATP-gated membrane pore, p2x 7(formerly p2z receptor) and A2a adenosine receptors are found to be predominantly expressed in T cells. The Gs-protein coupled A2a receptors activate cAMP-dependent protein kinase which was shown to have dual role in regulation of T cells functions. The results of our recent studies of adenosine receptors indicate that A2a receptors on T cell surface may play immunosuppressive role in conditions which lead to accumulation of extracellular adenosine. These conditions include pharmacological intervention with widely used anti-inflammatory drugs (methotrexate and sulfasalazine) and extracellular environment near large solid tumors. Hypoxic conditions in such tumors are known to cause accumulation of extracellular adenosine, which, in turn, as we have shown, could inhibit incoming antitumor cytotoxic T-lymphocytes from destroying the tumor. Normal development and functions of immune cells require adenosine deaminase (ADA) activity. Absence or low levels of ADA in humans result in severe combined immunodeficiency (SCID), which is characterized by hypoplastic thymus, T lymphocyte depletion, and autoimmunity. ADA SCID is currently explained only by intracellular lymphotoxicity of accumulated adenosine. We propose that T cell depletion, immunodeficiency, and autoimmunity could also be due to extracellular adenosine-induced signaling, which inhibits the antigen receptor (TCR) signaling and therefore affects the TCR-driven positive and negative selection of thymocytes. This, in turn, may lead to changes in antigen receptor repertoires and to immunodeficiency, Such properties of adenosine receptors suggest an expanded understanding of pathogenesis of ADA SCID as being due to two independent (intracellular and extracellular) mechanisms of adenosine action. It was conclusively demonstrated that functionally important T cell surface proteins including T cell receptor- are constitutively Ser/Thr phosphorylated on their ectodomains. We identified the major ecto-protein kinase activity in T-lymphocytes as casein kinase II-like (CKII-like) protein kinase. Consensus phosphorylation sites for serine and threonine protein kinases were found to

T细胞是天然抗病毒和抗癌免疫中的重要效应细胞。揭示T细胞分化和效应功能的细胞和分子要求是重要的。我们探索了抗原受体驱动的免疫过程的最终结果至少部分取决于不同组织中淋巴细胞胞外环境中生理上丰富的小信号分子。细胞外嘌呤(ATP和腺苷)及其(嘌呤能)受体是这类分子的一个例子。细胞外ATP和腺苷在免疫调节中的功能作用的研究已经发展为嘌呤能受体的单个分子和功能重要蛋白的细胞外结构域磷酸化的研究。atp门控膜孔,p2x 7(原p2z受体)和A2a腺苷受体主要在T细胞中表达。gs蛋白偶联A2a受体激活camp依赖性蛋白激酶,该蛋白激酶在T细胞功能调节中具有双重作用。我们最近对腺苷受体的研究结果表明,T细胞表面的A2a受体可能在导致细胞外腺苷积累的条件下发挥免疫抑制作用。这些情况包括使用广泛使用的抗炎药物(甲氨蝶呤和磺胺吡啶)进行药物干预,以及大型实体瘤附近的细胞外环境。已知在这种肿瘤中的缺氧条件会引起细胞外腺苷的积累,反过来,正如我们所展示的,可以抑制进入的抗肿瘤细胞毒性t淋巴细胞破坏肿瘤。免疫细胞的正常发育和功能需要腺苷脱氨酶(ADA)的活性。人类缺乏或低水平的ADA会导致严重的联合免疫缺陷(SCID),其特征是胸腺发育不全、T淋巴细胞耗损和自身免疫。ADA SCID目前只能通过细胞内积累的腺苷淋巴毒性来解释。我们提出T细胞耗损、免疫缺陷和自身免疫也可能是由于细胞外腺苷诱导的信号传导,它抑制抗原受体(TCR)信号传导,从而影响TCR驱动的胸腺细胞的阳性和阴性选择。反过来,这可能导致抗原受体的变化和免疫缺陷。腺苷受体的这些特性表明,ADA SCID的发病机制是由于腺苷作用的两种独立机制(细胞内和细胞外)而扩大的理解。最终证明,功能重要的T细胞表面蛋白,包括T细胞受体-在其外胞域上构成丝氨酸/苏氨酸磷酸化。我们发现t淋巴细胞中主要的外蛋白激酶活性是酪蛋白激酶ii样(ckii样)蛋白激酶。丝氨酸和苏氨酸蛋白激酶的一致磷酸化位点在α和β TCR链恒定区都具有很强的进化保守性。我们已经证明t细胞蛋白磷酸酶释放的ecto- or具有PP1和PP2a类蛋白磷酸酶的特性。这种外结构域的共价修饰可能通过影响tcr -多分子复合物的形成和抗原结合亲和力等方式改变T细胞同源相互作用。提示TCR外结构域磷酸化可能是调控TCR介导的t淋巴细胞反应的潜在机制。
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引用次数: 21
[Analysis of angiographic computed tomography with rapid helical scan. Clinical usefulness for the diagnosis of hepatocellular carcinoma]. 血管造影计算机断层快速螺旋扫描分析。肝细胞癌的临床诊断价值[j]。
Pub Date : 1998-10-01 DOI: 10.1272/jnms1923.65.367
A Kikkawa, T Ichikawa

Purpose: The aim of this study was to clarify the clinical usefulness of combined CT during arterial portography (CTAP), and CT arteriography (CTA), for the diagnosis of hepatocellular carcinoma.

Materials and methods: CTAP and CTA were performed in 58 patients with a combined 144 hepatocellular carcinoma (HCC) lesions. Arterial vascular access was obtained through bilateral punctures of the femoral artery with selective placement of catheters in the hepatic artery and superior mesenteric artery. CT scans were performed first during injection of contrast media into the superior mesenteric artery, followed by repeated imaging of the liver during injection of contrast media into the hepatic artery. Delayed CT (DCT) was also obtained 5 min after CTA.

Results: The detection rates for all 144 lesions were 73.6% with conventional contrast enhanced CT, 90.3% with CTAP, 95.8% with CTA, 87.5% with DCT, and 98.6% with combined CTAP and CTA. Of early HCC lesions (n = 18), 88.9%, 33.3%, 77.8%, 100%, and 88.9% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively. Of classical HCC lesions (n = 126), 71.4%, 98.4%, 98.4%, 85.7%, and 100% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively.

Conclusion: Combining CTAP and CTA improved the radiologist's ability to detect lesions with confidence and to differentiate perfusion abnormalities of HCCs.

目的:本研究的目的是阐明CT联合动脉门静脉造影(CTAP)和CT动脉造影(CTA)在肝细胞癌诊断中的临床价值。材料与方法:对58例144个肝细胞癌(HCC)病变行CTAP和CTA检查。通过双侧股动脉穿刺获得动脉血管通路,选择性地在肝动脉和肠系膜上动脉置入导管。首先在肠系膜上动脉注射造影剂期间进行CT扫描,然后在肝动脉注射造影剂期间重复肝脏成像。延迟CT (DCT)也在CTA后5分钟。结果:144例病变常规增强CT检出率为73.6%,CTAP检出率为90.3%,CTA检出率为95.8%,DCT检出率为87.5%,CTAP与CTA联合检出率为98.6%。在18例HCC早期病变中,常规增强CT、CTAP、CTA、DCT及CTAP和CTA联合检查的检出率分别为88.9%、33.3%、77.8%、100%和88.9%。经典HCC病变(n = 126)中,常规增强CT、CTAP、CTA、DCT及CTAP与CTA联合检出率分别为71.4%、98.4%、98.4%、85.7%和100%。结论:CTAP与CTA联合检查可提高放射科医师自信地发现病变及鉴别hcc灌注异常的能力。
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引用次数: 0
[Vasopressin and water metabolism]. 抗利尿激素与水分代谢。
Pub Date : 1998-10-01 DOI: 10.1272/jnms1923.65.392
Y Oiso
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引用次数: 0
Biological roles of vascular endothelial cell in various pathologic processes. 血管内皮细胞在各种病理过程中的生物学作用。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.265
G Asano, H Fukumoto, R Nishigaki, N Yamada, M Onda, Z Naito, M Yokoyama, T Ishiwata
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引用次数: 1
Veins of the lumbar spinal ganglia in human adults and fetuses. 成人和胎儿腰椎神经节静脉。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.298
M Takano, K Tanuma, H Ito, Y Shirai

To obtain a fundamental knowledge of the morphological relationship between nerve root symptoms and circulatory disorders, the distribution pattern of the veins in the lumbar spinal ganglia from the first to fifth vertebrae was investigated in 5 adult human cadavers (mean age 69.6 years) and 5 human fetuses (mean age 6.6 months). The following results were obtained: 1) In the adults the veins perforating from the outer surface of the fifth lumbar spinal ganglion were smaller in number than those perforating from the first to fourth ganglia. In contrast, in the fetuses the number of such veins was increased in the lower lumbar spinal ganglia. In each of the ganglia, the number of veins emerging through the dorsal side was much higher than the number perforating from the outer surface of the ventral sides. The veins perforating through the outer surface of the ganglion formed weak venous networks (periganglionic venous plexus) surrounding the dorsal ramus of the spinal nerve. 2) The veins communicating with the tributaries from the periganglionic venous plexus were classified into three types. Type 1 veins flowed into the intervertebral veins (the frequency ranged from 9.2 to 18.2 in the adults and from 22.4 to 37.0 in the fetuses). Type 2 veins coursed in the spinal cord along the dorsal root fibers and penetrated the dura mater on the way (the frequency ranged from 0.4 to 4.8 in the adults and from 1.2 to 2.2 in the fetuses). Type 3 veins opened directly into the internal vertebral plexus (the frequency ranged from 0.4 to 1.8 in the adults and from 0 to 0.4 in the fetuses). Type 1 veins were the most frequent among the three types of veins in both adults and fetuses. Few type 3 veins were observed in either group. 3) In the first and second lumbar vertebrae in the adults, three-quarters of each spinal ganglion was situated in the vertebral canal. In the lower lumbar region (L3-L5), three quarters of each spinal ganglion lay on the outside of the vertebral canal. In the fetuses, approximately one half to three-quarters of each lumbar spinal ganglion was located in the vertebral canal.

为了解神经根症状与循环系统疾病之间的形态学关系,我们对5具成人尸体(平均年龄69.6岁)和5例胎儿(平均年龄6.6个月)的第一至第五椎腰椎神经节内静脉的分布规律进行了研究。结果表明:1)成人从第5节外表面穿静脉的数量少于从第1节至第4节穿静脉的数量;相反,在胎儿中,这种静脉的数量在下腰椎神经节增加。在每个神经节中,从背侧穿出的静脉数量远远高于从腹侧外表面穿出的静脉数量。穿过神经节外表面的静脉在脊神经背支周围形成弱静脉网络(神经节周围静脉丛)。2)与神经节周围静脉丛支流相通的静脉分为三类。1型静脉流入椎间静脉(成人为9.2 ~ 18.2次,胎儿为22.4 ~ 37.0次)。2型静脉在脊髓内沿背根纤维走行,并在途中穿透硬脑膜(成人的频率为0.4 ~ 4.8,胎儿的频率为1.2 ~ 2.2)。3型静脉直接进入椎丛内部(成人的频率为0.4 ~ 1.8,胎儿的频率为0 ~ 0.4)。在成人和胎儿的三种静脉类型中,1型静脉最为常见。两组均未见3型静脉。3)在成人第一、第二腰椎,每个脊髓神经节的四分之三位于椎管内。在下腰椎区(L3-L5),每个脊髓神经节的四分之三位于椎管外侧。在胎儿中,每个腰椎神经节大约有一半到四分之三位于椎管内。
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引用次数: 1
[Removal of bile duct stones by endoscopic papillary balloon dilatation (EPBD) of papilla of Vater]. [内镜下乳头球囊扩张术(EPBD)取胆管结石]。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.328
E Uchida, M Onda, T Tajiri, T Kobayashi, T Aimoto, Y Nakamura, S Yamamura, A Matsushita, K Yanagi, Y Ogawa, Y Arima, K Egami, K Yamashita
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引用次数: 0
Successful treatment of anomalous origin of the left coronary artery from the pulmonary artery in a 5-week-old male infant. 成功治疗1例5周大男婴左冠状动脉起源于肺动脉的异常。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.312
M Kamisago, S Ogawa, Y Hino, O Jimbo, Y Nagai, R Hayashi, T Seki, T Ohkubo, J Zhang, H Yamauchi, J Ninomiya, M Yamamoto

A 5-week-old male infant who was referred to our hospital because of tachypnea and poor feeding. An electrocardiogram showed a deep Q wave in lead aVL, negative T waves in leads I, II, III, aVF and V6 and a positive T wave in VL. Echocardiography revealed severely impaired left ventricular function. Aortography confirmed with a diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Takeuchi's procedure was performed and the patient maintained postoperatively on assisted circulation for 7 hours even though sternal closure delayed until 7 days post operatively. His left ventricular function showed and marked improvement gradually.

一个5周大的男婴因呼吸急促和喂养不良被转介到我们医院。心电图示aVL导联深Q波,1、2、3、aVF、V6导联负T波,VL正T波。超声心动图显示左心室功能严重受损。主动脉造影证实左冠状动脉起源于肺动脉异常(ALCAPA)。采用Takeuchi手术,患者术后维持辅助循环7小时,尽管胸骨闭合延迟至术后7天。他的左心室功能逐渐有明显改善。
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引用次数: 1
[Osteoporosis and the prevention of age-related fractures]. [骨质疏松症和年龄相关性骨折的预防]。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.324
T Takeuchi
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引用次数: 0
Effects of serum of streptozotocin-induced diabetic rats on vascular smooth muscle cell growth in vitro. 链脲佐菌素诱导糖尿病大鼠血清对体外血管平滑肌细胞生长的影响。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.284
R Wang, M Kudo, Z Naito, M Yokoyama, N Yamada, G Asano

This study was undertaken to biochemically and immunohistochemically clarify the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), fibroblast growth factor receptor (bFGFR), insulin-like growth factor-I receptor (IGF-IR) and vascular smooth muscle cell (VSMC) growth by using Streptozotocin (STZ) treated rat serum. At 12, 16, 24 weeks after STZ administration, blood sera were collected from STZ treated rats. STZ treated rat sera promoted much more vascular smooth muscle cel proliferation than control sera. IGF-I was increased in the sera of STZ treated rats. Also according to western blot analysis, the protein synthesis of bFGFR and IGF-IR in the VSMCs was increased in STZ treated rat sera. Immunohistochemically, bFGF, IGF-I and their receptors were much more localized in VSMCs in STZ treated rat sera than in control sera. These results suggest that the growth factors and their receptors produced in VSMCs in STZ treated rat serum may contribute to the proliferation of VSMCs in autocrine and paracrine patterns.

采用生化和免疫组织化学方法研究链脲佐菌素(STZ)对大鼠血清碱性成纤维细胞生长因子(bFGF)、胰岛素样生长因子- 1 (IGF-I)、成纤维细胞生长因子受体(bFGFR)、胰岛素样生长因子- 1受体(IGF-IR)表达及血管平滑肌细胞(VSMC)生长的影响。STZ给药后12、16、24周采集STZ治疗大鼠血清。STZ处理的大鼠血清比对照血清更能促进血管平滑肌细胞的增殖。STZ处理大鼠血清中igf - 1升高。western blot分析显示,STZ处理大鼠血清中VSMCs中bFGFR和IGF-IR的蛋白合成增加。免疫组化结果显示,STZ处理大鼠血清中bFGF、IGF-I及其受体在VSMCs中的定位明显高于对照组。这些结果提示,STZ处理大鼠血清VSMCs中产生的生长因子及其受体可能促进VSMCs以自分泌和旁分泌方式增殖。
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引用次数: 7
Combination of low back pain and previous low back pain and shoulder stiffness in construction employees. 建筑工人腰痛与既往腰痛和肩僵硬的结合。
Pub Date : 1998-08-01 DOI: 10.1272/jnms1923.65.307
Y Shirai, M Miyamoto, Y Genbun, K Kaneda

A postal questionnaire for the prevalence of low back pain was studied with relevance to stiffness of that shoulder and a history of low back disorders in construction employees. The percentage of clerical employees with low back pain was 31.3% and of field workers was 30.3%. Odds ratios representing a relative risk factor for low back pain relating to each age group showed 2.35 in the clerical and 2.10 in the field workers at the age of 30-34 years, and 3.34 and 2.58 at the age of 35-39 years, respectively. In the persons with positive previous low back pain, the prevalence rate of low back pain was 52.6% in the clerical, and 50.2% in the field workers. Odds ratios for low back pain relating to previous low back pain significantly exceeded unity for the clerical employees (OR = 9.53) and the field workers (OR = 10.28), compared to those without a history of previous low back pain. The incidence of stiffness of the shoulder was 48.2% in the clerical and 45.2% in the field workers, and the prevalence rate of low back pain among those with stiffness of the shoulder was 68.5% in the clerical and 65.8% in the field workers. Odds ratio were 3.03 in both groups. Among each age group, the prevalence rate of stiffness of the shoulder with low back pain increased gradually to a maximum in the 45-49 age group of 19%, and then dropped. In those with a history of low back pain and/or stiffness of the shoulder, the prevalence of low back pain showed significantly greater value than other risk factors.

一份关于腰痛患病率的邮寄问卷,研究了建筑工人肩关节僵硬程度和腰痛病史的相关性。文职人员腰痛的比例为31.3%,现场工作人员为30.3%。代表各年龄组腰痛相对危险因素的比值比显示,30-34岁的文职人员和现场工作人员的比值比分别为2.35和2.10,35-39岁的比值比分别为3.34和2.58。在既往腰痛阳性人群中,文职人员腰痛患病率为52.6%,野外工作人员腰痛患病率为50.2%。与没有腰痛史的人相比,文职员工(OR = 9.53)和现场工作人员(OR = 10.28)与既往腰痛相关的腰痛的比值比明显超过统一。肩关节僵直的发生率分别为48.2%和45.2%,肩关节僵直人群腰痛患病率分别为68.5%和65.8%。两组的优势比均为3.03。各年龄组肩关节僵硬伴腰痛的患病率逐渐升高,45-49岁最大,为19%,随后下降。在有腰痛和/或肩关节僵硬史的患者中,腰痛的患病率明显高于其他危险因素。
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引用次数: 4
期刊
Nihon Ika Daigaku zasshi
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