肾癌DC-CIK 免疫治疗对相关细胞因子的影响

目的:检测树突状细胞(DC)联合细胞因子诱导的杀伤细胞(CIK)免疫治疗对肾癌患者术后外周血中细胞因子含量变化的影响。方法:术后随访我院2016年9月到2018年9月确诊的60例肾癌患者,对其给予DC-CIK免疫治疗,在治疗前一周和治疗后两周取外周血,通过酶联免疫检测法检测其外周血中IFN-γ、IL-2、IL-10等细胞因子水平,测定外周血中T淋巴细胞的亚群百分比,记录回输过程中的副作用及评估患者的生活质量。结果:治疗两周后,外周血中IFN-γ、IL-2水平提高,CD3~+、CD4~+T淋巴细胞含量增加,IL-10水平下降,CD8~+T淋巴细胞含量明显减少。患者毒副反应减少,生活质量得到明显改善。结论:DC-CIK细胞免疫治疗能够明显改善肾癌患者免疫失衡状态,提高患者免疫功能。     

生长抑素对猕猴肠缺血再灌注后回肠黏膜IFN-γ的影响

探讨生长抑素(somatostatin,SST)对肠缺血再灌注(intestinal ischemia reperfusion injury,IIR)后回肠黏膜IFN-γ产生及IIR免疫炎症损伤的影响。取15只健康猕猴分为正常对照、IIR、SST+IIR三组(n=5),ELISA检测回肠组织、肠上皮细胞、肠淋巴细胞、肠淋巴细胞孵育上清液、外周血、门静脉血中IFN-γ的水平;免疫组化检测IFN-γ、CD4、CD8、CD57的分布,图像分析软件测定阳性面积及IOD值。发现,IIR后回肠黏膜上皮细胞、门静脉血内IFN-γ水平较正常组显著增加[分别为(30.7±20.1)pg/mg和(9.4±2.4)pg/mg总蛋白;(18.1±1.1)pg/ml和(8.7±1.3)pg/ml](P<0.05),而肠淋巴细胞及其上清液的IFN-γ水平较正常组明显降低[分别为(1.7±0.02)pg/mg和(11.1±4.0)pg/mg总蛋白;(2.2±0.3)pg/mg和(5.2±1.5)pg/mg](P<0.05);预防性给予SST后,与IIR组比较,回肠上皮细胞及门静脉血内IFN-γ的水平显著下降[分别为(13.6±4.9)pg/mg总蛋白,P=0.055;(8.9±2.5)pg/ml,P<0.05],肠淋巴细胞及其上清液的IFN-γ水平无明显变化。组织匀浆及外周血的IFN-γ水平在三组间无明显差别。CD4+细胞、CD57+细胞分布与IFN-γ无关,CD8+细胞分布与IFN-γ变化趋势相反。因之,SST负性调控IIR时回肠上皮细胞IFN-γ的产生,从而可能阻止多器官功能障碍的发生发展。     

经导管动脉栓塞化疗联合射频消融和细胞因子诱导的杀伤细胞输注治疗小肝癌

目的 探讨经导管动脉栓塞化疗(TACE)联合射频消融(RFA)后行自体细胞因子诱导的杀伤细胞(CIK)输注治疗对小肝癌的疗效.评价CIK细胞过继免疫治疗后患者免疫指标的变化.方法 2004年2月至2006年2月本院收治的小肝癌患者43例,分为两组,所有患者均行TACE联合RFA治疗.其中研究组患者21例,均完成4次以上自体CIK细胞输注治疗,每次回输CIK细胞的数量为(1.1～1.5)×1010m,检测研究组患者在CIK治疗前后外周血T淋巴细胞亚群及NK细胞水平的变化;对照组患者22例,未行CIK细胞过继免疫治疗.两组患者均每1～2个月评价肿瘤情况.结果 (1)对照组治疗后第1、2和3年的肝内累积复发率分别为9.1%、22.3%和27.3%;术后1、2和3年的生存率分别为95.5%、81.8%和68.2%.研究组第1、2和3年的肝内累积复发率分别是9.5%、14.3%和19.0%;术后1、2和3年的生存率分别为95.2%、85.7%和76.2%.两组生存率差异无统计学意义(P=0.558).(2)研究组CIK细胞治疗前后外周血T淋巴细胞亚群检测显示CD3+、CD4+、CD56+(NK)效应细胞的比例和CD4+/CD8+比值显著上升(P<0.05),CD8+和CD3+CD56+效应细胞比例下降(P<0.05).结论 TACE序贯联合RFA和CIK细胞过继免疫细胞治疗小肝癌可以提高患者的机体免疫水平,可能对降低肿瘤复发,延长小肝癌患者的生存期有一定作用.     

自体肿瘤抗原致敏的树突状细胞联合细胞因子诱导的杀伤细胞治疗晚期肾癌的疗效观察

目的探讨负载自体肿瘤抗原的树突状细胞(DC)联合细胞因子诱导的杀伤细胞(CIK细胞)在晚期肾癌治疗中的临床疗效,并监测患者的免疫状态及不良反应。方法回顾分析2011-01/2013-12期间在我科治疗的82例晚期肾癌患者,单采其外周血单个核细胞(PBMC),其中贴壁细胞经体外诱导产生DC,并负载自体肿瘤细胞裂解物(Ag)制备Ag-DC;T淋巴细胞经体外诱导产生CIK细胞,将Ag-DC与CIK细胞共培养制备Ag-DC-CIK瘤苗,检测DC表面分子的表达及IL-12的分泌,监测CIK细胞增殖情况,并将Ag-DC-CIK分次回输给其中41名患者,以41例单纯的CIK细胞治疗作为对照,治疗2疗程后,检测患者外周血细胞因子水平及T细胞亚群变化,结合影像学等检查综合评价疗效,同时观察不良反应。结果负载肿瘤细胞冻融抗原的DC,高表达CD11c、CD83、CD86、HLA-DR表面分子,IL-12的分泌显著增加。Ag-DC与CIK细胞共培养后,可明显刺激CIK细胞的增殖,同时CD3+CD8+细胞及CD3+CD56+细胞的含量明显增加,此外,Ag-DC-CIK瘤苗的临床疗效明显高于单纯CIK细胞治疗组,2组均未发生严重的不良反应。结论晚期肾癌PBMC来源的DC负载自身肿瘤细胞冻融抗原能提高晚期肾癌患者的免疫状态。     

DC-CIK联合化疗治疗结肠癌的临床研究

目的:研究树突状细胞(Dendritic cells,DCs)和细胞因子诱导的杀伤细胞(Cytokine induced killer,CIK)联合化疗治疗结肠癌的临床疗效和免疫功能变化。方法:将40例入选病例随机分为单纯化疗组和联合治疗组,化疗组20例,仅行化疗[奥沙利铂(Oxaliplatin)+亚叶酸钙(CF)+5-氟尿嘧啶(5-FU)];联合组20例,给予DC-CIK联合化疗[奥沙利铂+亚叶酸钙+5-氟尿嘧啶]。比较两组患者治疗后局部复发率、生存率和毒性反应。流式细胞术检测T细胞亚群的比例、ELISA法检测细胞因子表达水平。评价DC-CIK免疫治疗的安全性。结果:联合组治疗后局部复发率低于化疗组(P<0.05),1、2年生存率高于化疗组,无明显差异(P>0.05)。化疗组治疗后外周血中CD8+比例升高,CD4+/CD8+比值下降,IL-6升高(P<0.05);而联合组治疗后外周血中CD4+、CD16+、CD56+、CD4+/CD8+比值显著升高,CD4+CD25+调节性T细胞比例显著下降,IFN-γ显著升高(P<0.05),联合组患者治疗后周围神经毒性、胃肠道反应明显轻于化疗组(P<0.05)。DC-CIK细胞回输过程中及回输后未见明显不良反应。结论:DC-CIK免疫治疗联合化疗,有可能降低术后复发和转移,提高结肠癌患者的免疫功能,减轻毒性反应,具有较高的安全性。     

单次大剂量与多次小剂量输注CIK治疗鼠肠癌效应的实验研究

探讨细胞因子诱导的杀伤细胞(cytokine-induced killer cell,CIK)单次大剂量与分次小剂量输注两种治疗模式的抗肿瘤的作用。建立BALB/c小鼠结肠癌模型;体外诱导培养小鼠CIK细胞,7天后CIK单次大剂量组荷瘤鼠接受总剂量为1×107的CIK细胞一次性输注;CIK分次小剂量组荷瘤鼠分5次(隔天1次)接受总剂量与单次组相同的CIK细胞输注,绘制肿瘤生长曲线;治疗后第14天,采用流式细胞术检测各治疗组小鼠脾细胞CD3+、CD4+、CD8+、NK1.1+、DX5+等细胞表型;建立CIK治疗后小鼠脾细胞对C26皮下移植瘤的预防和治疗模型,预防模型统计一周出瘤率,治疗模型生存资料分析采用Kaplan-Meier法及log-rank检验;ELISPOT法检测小鼠脾淋巴细胞经C26抗原刺激后分泌IFN-γ的能力。结果CIK单次治疗组小鼠肿瘤生长平均体积(253.30±43.59)mm3明显小于CIK分次治疗组(384.36±43.59)mm3,差异有统计学意义(P=0.042);CIK单次治疗组小鼠脾细胞相对于CIK分次治疗组、PBS对照组对C26结肠癌移植瘤表现出更好的预防和治疗效应(P0.05);CIK单次治疗组小鼠脾细胞较其余各组CD4+T细胞比例下调,而CD8+T细胞比例上调,差异有统计学意义(P0.05),而CD3+、NK1.1+、DX5+等细胞表型各组之间差异无统计学意义(P0.05);CIK单次治疗组小鼠脾细胞在经C26抗原刺激后分泌IFN-γ的能力最强,差异较其余各组有统计学意义(P0.05)。提示CIK单次大剂量输注较分次小剂量输注对BALB/c皮下结肠癌(C26)荷瘤小鼠具有更好的激发机体免疫应答效应以及肿瘤预防和治疗作用。     

氟尿嘧啶联合CIK细胞在小鼠结肠癌模型中抗肿瘤效应的研究

探讨氟尿嘧啶(5-FU)、CIK细胞以及5-FU联合CIK细胞对小鼠结肠癌移植瘤生长的作用,为临床上联合应用5-FU和CIK细胞治疗结肠癌提供理论依据。建立BALB/C小鼠结肠癌模型,在体外诱导培养小鼠CIK细胞,5-FU(12.5mg/kg,d0)联合CIK细胞(1×107,d3)处理小鼠结肠癌荷瘤模型,并绘制肿瘤生长曲线,生存分析采用Kaplan-Meier法及logrank检验,应用流式细胞仪分析荷瘤鼠肿瘤组织中淋巴细胞CTLA-4和非淋巴细胞CD80、CD86表达;RT-PCR法检测肿瘤组织中IFN-γ和TNF-α表达量。5-FU联合CIK细胞治疗组小鼠肿瘤生长速度明显慢于单治疗组,差异有统计学意义(P<0.05);5-FU处理后小鼠移植瘤组织中CD45+细胞表面CTLA-4表达量提高,且CD45-细胞CD80和CD86表达量增加;5-FU联合CIK细胞治疗可提高肿瘤组织IFN-γ与TNF-α表达量,且联合治疗组与单治疗组中IFN-γ的表达量之间的差异有统计学意义(P<0.05)。5-FU联合CIK细胞治疗对结肠癌移植瘤生长的抑制作用大于单独应用5-FU或CIK细胞,且可提高BALB/C小鼠结肠癌模型免疫功能。     

SARS S DNA疫苗不同免疫方案诱导细胞免疫应答的影响

目的观察SARS S DNA疫苗经不同的免疫途径及免疫次数,所诱导的免疫效果之间的差异。方法 C57BL/6小鼠经肌肉和皮下途径初次或加强免疫SARS S DNA疫苗,取其脾和肺淋巴细胞经S抗原多肽刺激以后,应用ELISA、ELISPOT和FACS等检测诱导细胞产生细胞因子情况。结果肌肉初次免疫后产生IFN-γ的量较低(均值脾:2.7 pg/ml;肺:68.9 pg/ml),加强免疫2次或3次后IFN-γ水平明显提高(脾:809.2～1398.7 pg/ml;肺:202.3～534.6 pg/ml),与初次免疫比较差异有统计学意义(脾P<0.001,肺P<0.05)。皮下二次免疫后IFN-γ产生量为54.3～106.1 pg/ml,但三次免疫后IFN-γ量显著提高均值达到729.1 pg/ml与对照组比较P<0.05。二次免疫后抗原特异性阳性细胞的频率肌肉免疫(188个/2×105细胞)高于皮下免疫(57个/2×105细胞),两者差异有统计学意义(P<0.05),而免疫3次后2种免疫途径可诱导数量相当的特异性阳性细胞(169～198个/2×105细胞,P>0.05)。S抗原特异性CD4+T细胞亚群以分泌IL-2为主,而抗原特异性CD8+T细胞分泌IFN-γ为主。结论经肌肉和皮下2种途径注射SARS S DNA疫苗免疫后,均可诱导小鼠产生特异性细胞免疫应答;加强免疫后诱导免疫应答明显强于初次免疫;肌肉免疫两次或皮下免疫三次后可达最佳免疫效果。     

CIK细胞回输联合吉西他滨和顺铂治疗鼻咽癌放疗后肝肺转移瘤的效果及机制研究

目的: 观察评价细胞因子诱导杀伤(CIK)细胞回输联合吉西他滨和顺铂(GP)方案化疗治疗鼻咽癌放疗后肝肺转移瘤的近远期疗效,并探讨其机制。方法: 2007年8月至2008年7月放疗后随访发现肝或肺转移患者30例,随机分为3组。研究1组10例行过继性CIK细胞回输联合GP化疗;研究2组10例行单纯GP化疗。对照组患者及健康志愿者各10例,不给予抗肿瘤治疗而仅进行随访。观察其近远期疗效、血清EB病毒DNA PCR定量和外周血淋巴细胞亚群分布变化。结果: CIK+GP组有效率(90%)比单纯GP组(70%)好,但2组间无明显差异;而CIK+GP组和GP组均比对照组(10%)好,差异明显。CIK+GP组最和GP组治疗后血清EBV-DNA PCR定量均有不同程度的下降,尤以CIK+GP组为明显,而对照组则无明显改变。鼻咽癌放疗后肝肺转移瘤患者外周血CD3⁺比例较健康志愿者显著低下,经CIK+GP治疗后CD3⁺比例较单纯GP化疗组有所提高;肝肺转移瘤患者和健康志愿者CD4⁺/CD8⁺比例无明显差异,经CIK+GP生物化疗后其比例明显升高,而经GP化疗后明显降低,2组之间存在明显差异。CIK+GP组、GP组和对照组2年生存率(OS)分别为60.0%、40.0%和20.0%,生存曲线分析显示3组病例之间均有明显差异(P＜0.05)。结论: CIK 细胞回输联合GP 化疗治疗鼻咽癌放疗后肝肺转移瘤具有肯定的近远期疗效并可改善其预后;两者具有协同作用,其作用可能与改变CD3⁺及CD4⁺/CD8⁺比例有关。     

脐血来源间充质干细胞可抑制异体T细胞的反应

目的研究脐血间充质干细胞(HUCB-MSCs)对异体T细胞的抑制作用。方法体外培养HUCB-MSCs,流式细胞术测表面标记;取正常人外周血,免疫磁珠分离CD3+T细胞,将分离的CD3+T与HUCB-MSCs 1∶1混合培养5 d,PHA刺激或不刺激,采用3H-TdR掺入法观察T细胞增殖,ELISA方法检测细胞因子,流式细胞术观察细胞凋亡。结果 HUCB-MSCs呈纺锤样的细胞形态,不表达CD14、CD34、CD45、HLA-DR,而表达CD29、CD44、HLA-ABC。HUCB-MSCs抑制PHA引起的T细胞增殖(5 230±550 vs 10 500±800 counts/min,P<0.001);HUCB-MSCs还能抑制异体T细胞分泌IFN-γ(510±60 vs 1 580±100 pg/mL,P<0.001)和TNF-α(590±20 vs 1 180±30 pg/mL,P<0.001),上调IL-4(16.3±8.2 vs 4.1±1.8 pg/mL,P<0.001)和IL-10(105±5 vs 17±2 pg/mL,P<0.001)分泌;HUCB-MSCs不诱导T细胞的凋亡。结论 HUCB-...     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.