外源性五羟色胺大鼠肺出血模型及其与浓度关系

目的通过外源性五羟色胺(5-HT)气管滴入建立新生大鼠肺出血模型及其与浓度关系.方法模型制作:日龄4～5天Wistar二级大鼠50只,随机分为4组:生理盐水对照组(A组)及3种不同浓度外源性5-HT实验组(B、C、D组):经气管导管分别滴入生理盐水和不同浓度5-HT,4小时后处死,观察肺大体及组织病理改变,将肺出血程度分为5级:Ⅰ正常;Ⅱ肺水肿;Ⅲ点状肺出血;Ⅳ局灶性肺出血;Ⅴ弥漫性肺出血,选择出制作肺出血模型的最佳的浓度.结果不同浓度5-HT气管内滴入均能引起不同程度肺出血,但随着浓度增加,B、C、D三组间的肺出血程度无差异(p＞0.05),其中 D组死亡率30%,对照组及B组和C组均无死亡,死亡鼠肺为弥漫性出血.结论 5-HT可致大鼠肺出血,以1×10-5mol/ml浓度为宜,随着5-HT浓度增加,大鼠死亡率增加,但肺出血发生率无差异.     

外源性降钙素基因相关肽预防内皮素-1致新生鼠肺出血的实验研究

目的　通过动物实验初步了解外源性降钙素相关肽 (CGRP)对预防性拮抗内皮素 - 1(ET - 1)致肺出血的作用 .方法　①使用新生Wistar乳鼠经气道分别给予高、中、低三种不同浓度的外源性CGRP ,了解其与肺出血的相关性 ;②将 4 0只乳鼠随即分成 4组 ,对照组先用生理盐水气道给药 ,实验组分别给予高、中、低三种不同浓度的外源性CGRP ,观察 1小时后每组再经气道给予外源性ET - 1,观察不同组间肺病理改变 .结果　①使用从浓度 6 .7× 10 -10mol/L～ 6 .7× 10 -6mol/L的外源性CGRP的实验组病理改变与对照组组间比较差异无显著性 (p >0 .0 5 ) .②经高浓度CGRP预处理的肺内滴入ET - 1后肺组织损伤程度最轻 .结论　外源性CGRP没有肺出血的影响并且可以预防性拮抗ET - 1致肺出血的反应 .     

骨髓间质干细胞在大鼠肺损伤模型中的表达及作用

目的研究外源性骨髓间质干细胞（BMSCs）在博来霉素（BLMA5）所致的大鼠肺间质纤维化模型中的表达及其治疗作用。方法将雌性60只SD大鼠随机分为4组,A组气管内滴注0.3ml生理盐水,B组气管内滴注相同体积BLMA5制作肺间质纤维化模型,C、D两组分别于气管内滴注相同体积BLMA5、生理盐水24h后,通过尾静脉将4,6-联脒-2-苯基吲哚（DAPI）标记BMSCs输入体内。分别于第7、14、28d每组各处死5只大鼠,行HE及Masson染色,并且在荧光显微镜下检测DAPI标记阳性细胞,分析肺内羟脯氨酸（HYP）含量。结果在各时间点,C组肺泡炎及肺间质纤维化评分均较B组减少（P〈0.05）,B组在第7d,HYP含量开始升高;第28d最高,显著高于A组C组（P〈0.01）;肺冰冻切片中C组在各时间点均见到DAPI阳性的细胞,D组偶见DAPI阳性的细胞。结论骨髓间质干细胞可定植于受损肺组织,并能有效阻止肺间质纤维化的进展。     

骨髓间质干细胞在大鼠肺损伤模型中的表达及作用

目的 研究外源性骨髓间质干细胞(BMSCs)在博来霉素(BIMA5)所致的大鼠肺间质纤维化模型中的表达及其治疗作用.方法 将雌性60只SD大鼠随机分为4组,A组气管内滴注0.3ml生理盐水,B组气管内滴注相同体积BLMA5制作肺间质纤维化模型,C、D两组分别于气管内滴注相同体积BLMA5、生理盐水24h后,通过尾静脉将4,6-联脒-2-苯基吲哚(DAPI)标记BMSCs输入体内.分别于第7、14、28d每组各处死5只大鼠,行HE及Masson染色,并且在荧光显微镜下检测DAPI标记阳性细胞,分析肺内羟脯氨酸(HYP)含量.结果 在各时间点,C组肺泡炎及肺间质纤维化评分均较B组减少(P<0.05),B组在第7d,HYP含量开始升高;第28d最高,显著高于A组C组(P<0.01);肺冰冻切片中C组在各时间点均见到DAPI阳性的细胞,D组偶见DAPI阳性的细胞.结论 骨髓间质干细胞可定植于受损肺组织,并能有效阻止肺间质纤维化的进展.     

外源性降钙素基因相关肽预防内皮素-1致新生鼠肺出血的实验研究

目的通过动物实验初步了解外源性降钙素相关肽(CGRP)对预防性拮抗内皮素-1(ET-1)致肺出血的作用.方法①使用新生Wistar乳鼠经气道分别给予高、中、低三种不同浓度的外源性CGRP,了解其与肺出血的相关性;②将40只乳鼠随即分成4组,对照组先用生理盐水气道给药,实验组分别给予高、中、低三种不同浓度的外源性CGRP,观察1小时后每组再经气道给予外源性ET-1,观察不同组间肺病理改变.结果①使用从浓度6.7×10-10mol/L～6.7×10-6mol/L的外源性CGRP的实验组病理改变与对照组组间比较差异无显著性(p>0.05).②经高浓度CGRP预处理的肺内滴入 ET-1后肺组织损伤程度最轻.结论外源性CGRP没有肺出血的影响并且可以预防性拮抗ET-1致肺出血的反应.     

核因子-κB活化与细胞因子的平衡在实验性肺间质纤维化中的作用

特发性肺间质纤维化是一种原因不明的间质性肺炎,发病的机制不清,尚无有效的治疗方法。本研究探讨特发性肺纤维化过程中NFκB(nuclearfactorκB,NFκB)的活化与TH1TH2细胞因子平衡之间的关系。选用C57BL6CrSlc小鼠,试验分为5组:A组(对照组):气管内滴入等量的生理盐水;B组:气管内滴入博莱霉素A55mg kg建立肺纤维化模型;C组:气管内滴入博莱霉素前6h和滴入后5d分别经尾静脉注射P65反义寡核苷酸900μg只;D组:气管内注入博莱霉素后1d和后5d分别经尾静脉给予P65反义寡核苷酸900μg只。E组(甲基强地松龙组):分别于气管内注入博莱霉素前和…     

重组IL-12腺病毒载体对肺炎小鼠NK细胞功能的影响

目的:探讨重组IL-12腺病毒载体(AdCMV IL-12)对肺炎小鼠NK细胞功能的影响.方法:90只BALB/c小鼠随机分为4组,A组:空白对照组15只,不给予病毒,滴鼻生理盐水.B组:对照组25只,每只鼻腔滴入10~5TCID_(50)/0.1 mL的Ad3悬液100 μL.C组:AdCMV IL-12组25只,每只鼻腔滴入10~5TCID_(50)的Ad3/0.1 mL悬液100 μL,3 d后滴鼻给药吸入AdCMV IL-12(5×10~8 PFU/只)100 μL.D组:AdCMVLacZ组25只,每只鼻腔滴入10~5TCID_(50)/0.1 mL的Ad3悬液100 μL,3 d后滴鼻给药吸入AdCMVLacZ(5×108 PFU/只)100 μL.开始滴入病毒定为0 d.于第5天,摘眼球取血,颈椎脱臼处死,无菌条件下取肺,用于转染及病毒毒力检测.无菌条件下取脾脏做NK细胞活性检测.测定血清IL-12及FIN-γ含量.结果:含有目的基因的腺病毒载体能有效转染支气管及肺组织并在局部表达目的基因.血清IL-12浓度为C组>A组>B组、D组,NK、FIN-γ浓度为C组>B组、D组>A组.病毒滴度:A组细胞生长良好.B、D组于10~(-4)出现细胞病变,C组于原液中出现病变.结论:重组IL-12腺病毒载体可通过滴鼻给药成功转染至肺组织,升高血液IL-12浓度,通过增加NK细胞活性而增加了IFN-γ的释放,从而导致病毒滴度下降,限制CVB病毒复制的作用.     

博来霉素致大鼠肺纤维化后神经营养因子4和酷氨酸激酶受体B表达及其意义

目的:探讨博来霉素致大鼠肺纤维化后神经营养因子4(NT4)和酷氨酸激酶受体B(Trk B)的表达及其意义。方法:用36只健康雄性SD大鼠,分为对照组和模型组,每组18只。对照组大鼠为气管内注射生理盐水,模型组大鼠按要求用博来霉素进行气管内灌注。两组大鼠分别于造模后第3、7和14 d各处死6只,取出肺组织,分别用Masson和HE染色检测肺纤维化程度。对照组和模型组大鼠中NT4及Trk B的含量用PCR和免疫组化检测,结果进行统计学分析。结果:与对照组比较,模型组造模后第3、7和14 d NT4和Trk B含量都有不同程度升高,并且随肺纤维化的严重程度而增高(P0.05),同时NT4和Trk B二者含量的升高呈正相关(r=0.568,P0.05)。结论:实验大鼠肺纤维化其肺组织中NT4和Trk B表达明显增加,表明NT4和Trk B可能参与肺纤维化的发生发展。这种改变可能与肺上皮细胞增生和Trk B/NT4轴信号传递受影响有关。     

落新妇甙对大鼠肺移植排斥反应的抑制作用

目的:探讨落新妇甙对大鼠肺移植排斥反应的抑制作用。方法:采用大鼠左侧单肺移植模型。随机将肺移植后的40只大鼠分为4组:A组肺移植后用生理盐水(1ml/天)灌胃,B组肺移植后用环孢素A(5mg/kg/天)灌胃,C组肺移植后用落新妇甙(1ml/kg/天)灌胃,D组肺移植后用环孢素A(2.5mg/kg/天)及落新妇甙(1ml/kg/天)灌胃。术后第10天切取移植肺观察肺急性排斥反应分级情况。结果:B组、C组及D组移植肺排斥反应分级均低于A组(P<0.05～0.01);D组移植肺急性排斥反应最轻,优于C组(P<0.05)和B组(P<0.01)。结论:落新妇甙对肺移植排斥反应有较强的抑制作用,并与环孢素A有协同作用。     

IL-37 抑制IL-18 在大鼠肺纤维化模型中的表达及意义的探讨

目的:初步研究博来霉素致肺纤维化大鼠肺组织中IL-37、IL-18 的表达水平,探讨其在PF 发生、发展中的表达及意义。方法:将45 只清洁级Wistar 大鼠按随机数字表法分为健康对照组(N 组)、博来霉素组(B 组)、地塞米松治疗组(D组),每组大鼠各15 只,B 组及D 组大鼠给予气管内注射博来霉素4 mg/ kg 制作肺纤维化模型,N 组给予相同体积生理盐水作为对照,D 组大鼠于肺纤维化造模基础上第2 天每日腹腔注射地塞米3 mg/ kg,N、B 组大鼠腹腔注射生理盐水作为对照。各组大鼠分别于造模后第7、14、28 天处死,HE 染色评价肺组织病理形态学变化,碱水解法及酶联免疫吸附法分别测定肺组织匀浆中羟脯氨酸(HYP)、IL-37 含量,RT-PCR 法测定肺组织中IL-18mRNA 表达量。结果: HE 染色显示B、D 组大鼠肺组织病理学改变由肺泡炎症逐渐发展为纤维化,B、D 组HYP 含量随时间推移逐渐升高,以第28 天为著(P<0.05);于B、D 组IL-37、IL-18mRNA 表达于第7 天升高至最高点,后逐渐降低,至第28 天均高于N 组,差异有统计学意义(P<0.05); D 组IL-37、IL-18mRNA 表达在同一时间均低于B 组(P<0.05)。结论:IL-37、IL-18 在大鼠肺纤维化发病早期起重要作用,可能参与了肺纤维化发生与发展。     

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.     

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.     

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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

'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.