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1.
目的和方法:采用分离的Sprague-Dawley大鼠心室肌细胞,以Fura-2/AM荧光指示剂负载,检测心肌细胞内游离钙浓度([Ca2+]i)变化,探讨内皮素-1(ET-1)对[Ca2+]i的作用及其机制。结果:ET-1(1×10-7mol/L)引起[Ca2+]i升高分两个时相:快速相和持续相,可被ETA的特异性受体阻断剂BQ123(2×10-6mol/L)所阻断。移去细胞外液钙以及用百日咳毒素(200ng/mL)处理10h后,ET-1仍引起快速相,但持续相消失。Ryanodine(4μmol/L)和异搏定(2×10-5mol/L)对ET-1诱导[Ca2+]i升高的作用无显著影响。结论:ET-1升高[Ca2+]i是通过ETA受体介导;快速相[Ca2+]i升高主要由胞内Ryanodine不敏感的钙池释放造成,与百日咳毒素敏感的G蛋白无关;持续相[Ca2+]i升高主要由胞外Ca2+内流引起,不是通过电压依赖性L-型钙通道介导,与百日咳毒素敏感的G蛋白有关  相似文献   

2.
目的:观察异丙嗪(promethazine,PMZ)对家兔EGTA性发热的影响并探讨其作用机制。方法:侧脑室和静脉给药。用Fura-2荧光分光光度法测定细胞内游离钙浓度([Ca2+]i)。结果:(1)侧脑室灌注06μmolEGTA引起家兔明显的发热反应,侧脑室灌注06μmolEGTA20min后,静脉注射PMZ(5mg/kg)明显抑制EGTA引起的结肠温度上升,其3h发热反应指数明显低于侧脑室灌注06μmolEGTA20min后静脉注射生理盐水(NS)组。而侧脑室灌注人工脑脊液(ACSF)20min后静脉注射PMZ(5mg/kg)组家兔结肠温度明显低于ACSF+NS对照组。(2)体外实验发现,向下丘脑细胞悬液中加入终浓度为074mmol/L的PMZ,下丘脑细胞[Ca2+]i从(1592±188)nmol/L升高到(5337±901)nmol/L(P<005)。结论:PMZ诱导体温调节中枢神经细胞[Ca2+]i升高可能是PMZ抑制家兔EGTA性发热的中枢机制之一。  相似文献   

3.
本文应用细胞膜放射标记和离子交换层析法测定巨噬细胞(MФ)内肌醇-1,4,5-三磷酸(IP3)、用Ca ̄(2+)指示剂的分光光谱法测定MФ内Ca ̄(2+)浓度([Ca ̄(2+)])、用APAAP桥联酶标法检测MФ表面Ia抗原的表达,研究去甲肾上腺素(NE)对大鼠腹腔的MФ内IP3、[Ca ̄(2+)]i和MФ表面la抗原表达的影响。结果显示NE(10 ̄(-8)mol/L)可显著增高MФ中IP_3含量(442±22cpm/10 ̄6cells,对照组102±8cpm/10 ̄6cells,P<0.01);NE可使MФ内[Ca ̄(2+)]i显著增高(322±78nmol/L,对照组97±17nmol/L,P<0.01);NE可显著增高MФ表面I-A、I-E抗原的表达(64±8%、58±6%,对照组50±3%,44±4%,P<0.01)。提示神经递质NE促进MФ表面Ia抗原表达的作用可能是通过第二信使IP_3和Ca ̄(2+)介导的。  相似文献   

4.
钙离子与牛磺酸两者跨心肌细胞膜内流的相互影响   总被引:1,自引:2,他引:1  
目的和方法:取新生SD大鼠心室肌制备培养搏动心肌细胞,采用放射性同位素45Ca2+及3H-牛磺酸示踪技术,观察钙离子与牛磺酸跨心肌细胞膜内流的相互影响。结果:(1)牛磺酸内流在低胞外Ca2+浓度([Ca2+]o,0.5mmol/L)和高[Ca2+]o(40mmol/L)均比正常[Ca2+]o(15mmol/L)和高[Ca2+]o(40mmol/L)时增加,尤以低[Ca2+]。时明显;异搏定(10μmol/L)能促进牛磺酸的内流;(2)10~20mmol/L牛磺酸对不同[Ca2+]。(05、15和40mmol/L)下的Ca2+内流均有抑制作用,而1mmol/L牛磺酸只抑制高[Ca2+]o时Ca2+内流,对低[Ca2+]o和正常[Ca2+]o时Ca2+内流无明显作用;1~20mmol/Lβ-丙氨酸对Ca2+内流无明显影响。结论:胞外Ca2+浓度的变化可直接影响牛磺酸内流,而牛磺酸能抑制Ca2+的内流,两者相互影响,从而发挥牛碘酸调节细胞内Ca2+浓度的作用  相似文献   

5.
用Fura-2作为荧光探针测定大鼠腹腔巨噬细胞(M)内钙离子浓度([Ca ̄(2+)]i),APAAP桥联酶标法检测M表面Ia抗原的表达。结果表明:5×10 ̄(-6)mol/L的乙酞胆碱(Ach)可使M[Ca ̄(2+)]i;明显上升,可促进M表面I-A和I-E抗原的表达,而阿托品(10 ̄(-5)mol/L)可阻断Ach升高[Ca ̄(2+)]i的作用。阿托品、三氟啦嚎(TFP,50μmol/L)、EGTA(6mmol/L)均可阻断M促进MIa抗原表达的作用,cAMP依赖性蛋白激酶抑制剂(PKI,25μg/ml)对Ach促进MIa抗原表达的作用无影响。  相似文献   

6.
目的和方法:本实验给孕期自发性高血压大鼠(SHR)服用卡托普利(Cap),观察对其子鼠动脉血管平滑肌细胞(VSMC)内钙离子浓度([Ca2+]i)、细胞生长、DNA合成的影响。结果:孕期给予Cap治疗,可使子代SHR动脉VSMC的[Ca2+]i明显低于不加处理的SHR对照组(208.37±31.34vs274.39±53.65)nmol/L,P<005;血清诱导下的细胞生长速度及DNA合成也显著受抑(P<001)。结论:胚胎形成期可能是SHR高血压发生、发展过程中的重要时期,在此期经Cap干预能够减弱其发病,降低应激状态下升压的易感性。  相似文献   

7.
为了研究谷氨酸致痫和人工合成的糖皮质激素地塞米松抑痫作用的细胞内机制,本文在EPC 9 光电联合检测系统上用Fura 2 阳离子检测法观察了地塞米松对谷氨酸引起的培养乳鼠海马神经细胞内[Ca2+ ]i 的影响。结果:(1)谷氨酸引起海马神经元内[Ca2+ ]i 显著升高,EGTA(5 m m ol/L)耗竭细胞外钙后,谷氨酸升钙作用消失,给予氯化钙(1 m m ol/L)后其升钙作用恢复:Verapam il(10 μm ol/L)对谷氨酸升钙作用无明显的影响,MK 801(10 μm ol/L,NM DA 受体特异性非竞争性阻断剂)可明显阻断谷氨酸的升钙作用。(2)地塞米松(100 μm ol/L)作用2 h 明显抑制了谷氨酸(200 μm ol/L)的升钙作用,地塞米松(100 μm ol/L)+ 放线菌酮(10 μm ol/L,蛋白合成抑制剂)共同作用2 h,再加入谷氨酸,则地塞米松的抑制作用消失,地塞米松(100 μm ol/L)作用2 m in 对谷氨酸(200 μm ol/L)的升钙作用无明显影响。本实验结果提示,谷氨酸通过NM DA 受体介导的外钙内流升高了海马神经元胞内[Ca2+ ]i,地塞米松可能通过基因组机制抑制了谷氨酸的这种升  相似文献   

8.
LFA-1和ICAM-1广泛表达于各胸腺细胞亚群,但ICAM-1在PNA ̄+细胞的表达下调。本文报道:用抗LFA-1/ICAM-1和抗CD3单抗,分析了粘附分子LFA-1/ICAM-1对抗CD3诱导的胸腺细胞[Ca ̄(2+)]i应答的影响。结果显示,可溶性抗LFA-1/ICAM-1可抑制ConA刺激的胸腺细胞增殖,且以抗LFA-1抗体的作用更为显著,在ConA或抗CD3诱导的胸腺细胞[Ca ̄(2+)]i应答中,抗LFA-1单抗可明显抑制[Ca ̄(2+)i升高。但如果用二抗交联CD3和LFA-1,胸腺细胞[Ca ̄(2+)i则显著高于单独交联CD3时的水平(P<0.01),而CD3与ICAM-l交联却无此效应,此外,仅交联LFA-1或ICAM-1也无诱导[Ca ̄(2+)]i应答的作用。提示在LFA-l与ICAM-1介导的胸腺细胞与胸腺基质细胞相互作用中,LFA-1可为TCR/CD3途径介导的胸腺细胞活化提供复合刺激信号。  相似文献   

9.
目的和方法:通过测定心肌细胞脂质过氧化水平及细胞内钙离子浓度,探讨了阿霉素中毒心肌细胞损伤机制与脂质过氧化及钙离子超负荷的关系。结果:中毒心肌细胞培养基中LDH释放量由250.2增加到853.7μmol/L,SOD活力由257.55(U/mg·pro)下降到185.88(U/mg·pro),丙二醛(MDA)含量由1.409(nmol/mg·pro)增加到1.638(nmol/mg·pro),细胞内游离钙浓度由240.18(nmol/L)增加到1460.40(nmol/L);阿霉素中毒早期仅有〔Ca2+〕i升高;中毒4h后出现脂质过氧化、心肌损伤加重及〔Ca2+〕i的进一步升高;结论:心肌细胞内〔Ca2+〕i早期增高是心肌损伤的始动环节,脂质过氧化与其诱导的〔Ca2+〕i进一步超负荷之间的恶性循环是心肌损伤加重的根本原因  相似文献   

10.
SRBC膜提取物对猪PBMNC第二信使的影响   总被引:2,自引:0,他引:2  
胰酶水解绵羊红细胞(SRBC)释放膜表面活性蛋白组分Ⅲ(TRF-Ⅲ),单独作用可使猪外周血单个核细胞(PBMNC)胞内cAMP水平升高,以100μg/ml浓度刺激达最高峰,由对照组0.94±0.14pmol/L升高到2.75±0.25pmol/L(P<0.01)。如果PBMNC事先与腺苷酸环化酶(ACase)抑制剂LiC1孵育后再以TRF-Ⅲ或PAH刺激。cAMP增高受到抑制(P<0.01);而EDTA-2Na(一种磷酸二酯酶PDE抑制剂)对此cAMP升高无影响。结果提示,此cAMP升高主要是通过活化ACase水解ATP生成cAMP,而不像是抑制PDE减少cAMP降解引起的。TRF-Ⅲ诱导猪PBMNC胞内Ca~(2+)浓度升高,以100μg/ml刺激2分钟升高最多,由对照组的242±7nmol/L升高到323±15nmol/L(P<0.01)。以EG-TA除去胞外Ca~(2+)再以TRF-Ⅲ或PAH刺激,仅观察到小范围[Ca~(2+)]i升高。看来这一过程包括了刺激胞内Ca~(2+)释放和胞外Ca~(2+)内流两种方式。以上结果证明,TRF-Ⅲ对淋巴细胞功能影响与细胞内第二信使有关。  相似文献   

11.
Renal dysplasia and asplenia in two sibs   总被引:2,自引:0,他引:2  
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.  相似文献   

12.
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.  相似文献   

13.
About 1900, modern food selection and processing caused widespread 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 panhypovitaminosis B, i.e., a mixture of substrate beriberi and substrate pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse 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 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.  相似文献   

14.
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.  相似文献   

15.
16.
Newton H 《Medical history》2011,55(2):153-182
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.  相似文献   

17.
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.  相似文献   

18.
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.  相似文献   

19.
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.  相似文献   

20.
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.  相似文献   

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