原发性胆汁性肝硬化PDC-E2特异性T细胞拮抗性模拟肽的筛选

目的筛选可拮抗原发性胆汁性肝硬化（PBC）中PDC-E2165-174特异性CTL功能的模拟肽.方法以自身抗原表位PDC-E2165-174（LLAEIETDKA）为原型肽,采用丙氨酸突变扫描法,通过亲和力分析及其对PDC-E2165-174特异性CTL细胞毒性和分泌细胞因子等功能的抑制效应,从中筛选拮抗性模拟肽.结果8条模拟肽中,5号位突变的模拟肽（I5A）显示与HLA-A＊0201分子高亲和力,5名PBC患者PDC-E2特异性CTL对其负载的T2细胞的杀伤率均小于10%,并且I5A也未能诱导PBC患者PDC-E2特异性CTL产生IFN-γ.在原型肽的存在下,I5A可抑制PDC-E2165-174 CTL细胞毒性和分泌IFN-γ,随着模拟肽浓度增加,抑制效应越强,在10 μmol/L浓度时可以明显抑制PDC-E2165-174 CTL的细胞毒活性和分泌IFN-γ的能力.结论模拟肽I5A（LIAEAETDKA）可能是PDC-E2165-174特异性CTL的一个拮抗性多肽,其抑制效应并不是其能竞争结合靶细胞上的HLA-A＊6201分子,而是对TCR的一种拮抗作用,为将来设计以TCR为基础的特异性免疫治疗提供实验依据.     

四聚体技术检测原发性胆汁性肝硬化患者血循环中抗原特异性T细胞

目的定量检测原发性胆汁性肝硬化(PBC)患者体内抗原特异性T淋巴细胞含量,探讨其在PBC发病机制中的作用。方法采用四聚体技术检测15例HLA-A0201阳性(A2 )PBC患者外周血单个核细胞(PBMC)经抗原肽诱导生长的细胞毒性T淋巴细胞(CTL)中PDC-E2159~167aa与PDC-E2165~174aa特异性CD8 T细胞频率,以A0201阴性(A2-)PBC患者与A2 的其他慢性肝病和健康自愿者为对照组。结果在A2 PBC患者PDC-E2159~167aa与PDC-E2165~174aa诱导的CTL中可检测到其相应的四聚体/CD8 细胞,平均频率分别为0.42%±0.24%(0.17%~1.08%)、0.27%±0.17%(0.05%~0.56%),各对照组的四聚体阳性细胞频率均低于0.1%,差异非常显著(P<0.001);A2 PBC组中PDC-E2159~167aa特异性的CTL频率与PDC-E2165~174aa特异性的CTL无显著性差异(P>0.05)。处于临床Ⅰ、Ⅱ期的A2 PBC患者中CD8 特异性CTL频率均较Ⅲ期的要高(P<0.05)。PDC-E2159~167aa特异性CTL与PDC-E2165~174aa特异性CTL频率在抗-PDC阳性PBC组和抗-PDC阴性组之间均无显著性差异(P>0.05)。结论HLA-A0201限制性的PDC-E2159~167aa和PDC-E2165~174aa特异性CD8 CTL在PBC疾病进展中起重要作用,抗线粒体抗体阴性或抗-PDC阴性PBC患者与阳性患者可能有着相似的T细胞介导的免疫发病机制。     

人工抗原提呈细胞的制备和应用的研究

目的 制备人工抗原提呈细胞（artificial antigen presenting cell,aAPC）并用它从HLA-A2阳性健康个体外周血单个核细胞（PBMC）中诱导和扩增特异性细胞毒性T淋巴细胞（CTL）.方法 将HLA-A2-EBV四聚体分子和抗CD28抗体分子吸附固定在细胞大小的聚苯乙烯乳胶微球（5μm）表面制成aAPC;采用流式细胞仪表型分析;aAPC和HLA-A2阳性个体人外周血单核细胞进行混合淋巴细胞反应;用HLA-A＊0201-EBV四聚体染色法检测特异性CTL的频率;应用细胞内细胞因子染色法检测特异性CTL功能性细胞因子IFN-γ的分泌;采用LDH释放法检测特异性CTL的特异杀伤活性.结果 流式细胞仪分析显示微球表面吸附有HLA-A2-EBV四聚体分子和抗CD28抗体分子;四聚体检测及细胞内细胞因子染色法检测与经典细胞毒试验结果一致,结果表明aAPC在体外可诱导抗原特异性CTL的生成.结论 aAPC制备成功,并在体外有效地诱导抗原特异性CTL的生成.     

人乳头状瘤病毒11型E7抗原HLA-A*0201限制性细胞毒性T淋巴细胞表位的功能鉴定

目的 筛选和鉴定人乳头状瘤病毒11型E7抗原(HPVllE7)HLA-A*0201限制性细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位.方法 预测HPVllE7抗原HLA-A*0201限制性CTL表位并合成相对应的表位多肽和四聚体(tetramer),即HPVllE7 7-15(TLKDIVLDL)、15-23(LQPPDPVGL)、47-55(PLTQHYQIL)、81-89(DLLLGTLNI)和82-90(LLLGTLNIV).从健康HLA-A*0201成人外周血单一核细胞诱导树突状细胞(DC)并负载上述表位多肽,流式细胞技术检测DC成熟分化标记及ELISA法检测DC分泌的IL-12;成熟DC负载各组多肽后观察DC激活T淋巴细胞的效应,ELISA法检测T细胞分泌的IFN-γ;四聚体检测抗原特异性CD8+ T细胞及乳酸脱氢酶(LDH)释放法评价DC诱导的CTL对靶细胞的特异性体外杀伤效应.结果 预测的5条HPVllE7表位多肽均能诱导DC的成熟分化;E7 7-15、82-90和15-23多肽负载的DC能激活T淋巴细胞分泌高水平IFN-γ;E7 7-15多肽负载的DC能刺激特异性tetramer+CD8+细胞增殖且其诱导的CTL对HPVllE7/293细胞产生高效率的特异性杀伤作用(P<0.05).结论 筛选并鉴定出1条HPVllE7HLA-A*0201限制性CTL表位E7 7-15(TLKDIVLDL),负载该表位肽的DC体外可诱导高效、特异性的CTL效应,抗原性较强,有可能作为HPV感染治疗用肽疫苗的候选表位.     

人锌转运蛋白8的HLA-A~*0201限制性CTL表位的预测及初步验证

目的预测和初步鉴定1型糖尿病(T1DM)主要自身抗原锌转运蛋白8(ZnT8)的HLA-A*0201限制性细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)表位,为基于ZnT8抗原表位的特异性免疫治疗奠定基础。方法选取BIMAS预测工具预测该抗原HLA-A*0201限制性结合肽,人工合成待测表位肽,利用T2细胞株测定各肽与HLA-A*0201分子的结合力。利用酶联免疫斑点检测(enzyme-linked immunospotassay,ELISPOT)方法检测候选肽刺激T1DM患者外周血单个核细胞分泌IFN-γ和IL-2的能力,利用标准51Cr释放试验检测特异性CTL诱导活性。结果在所筛选的5个候选CTL表位中,ZnT8(107-115)、ZnT8(115-123)及ZnT8(145-153)与HLA-A*0201分子具有较高的结合荧光强度,可在体外有效诱导抗原特异性CTL的产生,刺激T1DM患者PBMC分泌IFN-γ和IL-2,并对抗原肽负载的T2细胞具有明显的杀伤效应。结论 ZnT8(107-115)、ZnT8(115-123)及ZnT8(145-153)可能是HLA-A*0201限制性CTL表位,为基于人ZnT8抗原表位的特异性免疫治疗奠定理论基础。     

癌-睾丸抗原MAGEC2 HLA-A3限制性细胞毒性T淋巴细胞表位的鉴定

目的:预测并初步鉴定HLA-A3超型限制性MAGEC2抗原特异性细胞毒性T细胞(CTL)表位肽,为基于超型表位的MAGEC2治疗提供实验基础及新的候选靶标。方法:通过BIMAS、SYFPEITHI和IEDB软件预测打分来选取MAGEC2的HLA-A3限制性表位;结合力实验用于检测候选表位与T2A3细胞表面HLA-A3分子的结合能力,ELISPOT实验检测候选表位肽诱导的CTL分泌IFN-γ的能力,体外细胞毒实验检测侯选表位肽诱导的CTL杀伤靶细胞的能力。结果 :表位肽P147、P167、P196、P229和P251具有较好的HLA-A3结合力。ELISPOT实验结果显示表位肽P167、P196和P251诱导的CTL具有分泌IFN-γ的能力。细胞毒实验结果显示表位肽P196和P251诱导的CTL对靶细胞有一定的杀伤作用(P0.05或P0.01)。结论 :P196和P251有更高的HLA-A3分子亲和力,保留了原有的免疫原性,是优秀的MAGEC2抗原的HLA-A3限制性CTL候选表位,可以成为新的抗肿瘤多肽免疫治疗疫苗的候选表位。     

鼠胰岛素B链HLA-A*0201限制性CTL表位拮抗型改造肽的设计与鉴定

目的设计并鉴定具有负调致病细胞毒性T细胞(cytotoxic Tlymphocyte,CTL)免疫应答功能的改造肽配体(al-tered peptide ligand,APL),为基于胰岛素自身抗原的I型糖尿病特异性免疫治疗奠定基础。方法利用InSilico技术模拟构建TCR-pMHC(TCR-HLA-A*0201-mInsB5-14)复合物三维结构,根据结构选择改造位点P6;通过保守/不保守单个氨基酸虚拟替换得到若干候选APL;通过自由能变化计算、相对亲和力检测、细胞因子分泌水平检测等体外功能实验,初步鉴定具有拮抗效应的APL。结果筛选得到的APL mInsB5-14H6F(H→F)与天然肽mInsB5-14空间结构相似,能与HLA-A*0201分子结合,其HLA-A*0201分子的相对亲和力与mInsB5-14相近。该APL作用下mInsB5-14刺激CD8+T细胞分泌IFN-γ的水平明显低于天然肽单独刺激下特异性CTL分泌IFN-γ的水平(P0.05)。结论基于天然自身抗原表位mInsB5-14改造得到的mInsB5-14H6F是HLA-A*0201限制性的APL,该APL通过降低致病CTL特异性分泌IFN-γ的水平,可能诱导HLA-A*0201转基因NOD小鼠的自身耐受,从而为I型糖尿病治疗性疫苗的研发奠定了基础。     

骨髓瘤抗原Sp17 HLA-A*0201限制性CTL表位预测及初步鉴定

目的鉴定骨髓瘤抗原Sp17的HLA-A＊0201限制性CTL表位。方法采用超基序和量化基序法预测Sp17的HLA-A＊0201限制性CTL表位；用T2细胞亲和力实验和稳定性实验对该表位进行初步鉴定。结果超基序和量化基序法预测得出Sp17抗原的4个CTL表位（LLEGLTREI（19-27）、ILREQPDNI（27-35）、SLLEKREKT（45-53）、KEKEEVAAV（111-119）），亲和力实验结果表明LLEGLTREI（19-27）、ILREQPDNI（27-35）、SLLEKREKT（45-53）有较高亲和力，而KEKEEVAAV（111-119）肽亲和力较低；稳定性实验表明ILREQPDNI（27-35）、SLLEKREKT（45-53）与HLA-A＊0201分子结合稳定性较好。结论ILREQPDNI（27-35）、SLLEKREKT（45-53）有可能是骨髓瘤抗原Sa17 HLA-A＊0201限制件CTL表位。     

CD40配基化的肿瘤特异性树突状细胞介导Th1细胞分化的研究

目的：探讨CD40配基化的肿瘤特异性DCs在介导Th1细胞分化中的作用。方法：采用GM-CSF和IL-4联合方案体外诱导小鼠髓系DCs，并利用mCD40L-CHO和TNF-α分别刺激凋亡肿瘤细胞负载的DCs制备DCs瘤莆；^3H-TdR掺入试验检测DCs对T淋巴细胞的促增殖效应；ELISA测定细胞培养上清中IL-10、IFN-1、IL-12的含量；胞内染色和流式细胞术检测经成熟DCs活化的T细胞中CD4^＋IFN-γ^＋T和CD4^＋IL-4^＋T的比例。结果：体外刺激T细胞增殖能力在CD40配基化DCs组最高（P〈0．05），CD40配基化DCs能更有效地促进活化T细胞分泌IFN-γ和介导CD4^＋IFN-γ^＋T细胞的分化（P〈0．05）。同时，CD40配基化DCs分泌IL-12的量也明显高于TNF-α组（P〈0．05）。结论：CD40配基化的肿瘤特异性DCs体外能有效介导Th1细胞的分化。     

15d-PGJ2对肾小管上皮细胞CD40及RANTES表达的影响

目的：观察过氧化物酶体增殖物激活受体γ（PPARγ）激动剂15d-PGJ2对干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNF-α）诱导的人近端肾小管上皮细胞（HK-2）CD40和RANTES表达的影响。方法：体外培养人近端肾小管上皮细胞株，分组如下：（1）正常对照组；（2）IFN-γ（50μg／ml）组；（3）TNF-α（10ng／ml）组；（4）IFN-γ（50μg/ml）＋TNF—α（10ng／ml）组；（5）IFN-γ（50μg／ml）＋TNF-α（10ng／ml）分别加1、3、5μmol／L15d-PGJ2组；（6）IFN-γ＋TNF-α．刺激＋15d-PGJ2（5μmol／L）＋GW9662（PPARγ特异拮抗剂）1μmol／L组。GW9662和15d-PGJ2分别在IFN-γ和TNF-α刺激前3和2小时加入。分别采用RT-PCR、流式细胞仪（FACS）和酶联免疫法（ELISA）检测CD40和RANTES基因和蛋白的表达水平。结果：正常HK-2细胞中，CD40、RANTES有基础水平表达。IFN-γ能显著上调HK-2细胞CD40蛋白的表达；TNF-α单独刺激对CD40表达无显著影响，但能增强IFN-γ的刺激效应。IFN-γ＋TNF-α显著增加HK-2细胞RANTES的表达和分泌。15d—PGJ2呈剂量依赖式在基因和蛋白水平显著抑制IFN-γ＋TNF-α．诱导的CIMO和RANTES的表达。加入PPARγ特异拈抗剂GW9662后，能够部分逆转15d-PGJ，对CIMO和RANTES表达的抑制效应，但并不能完全阻断其作用。结论：15d-PGJ2部分通过PPARγ介导的信号途径参与抑制IFN-γ＋TNF-α．诱导的人近端肾小管上皮细胞CD40和RANTES的表达，从而在肾脏局部发挥免疫调节和抗炎作用。     

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.     

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.     

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.     

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.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.