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961.
Protein kinase was found to be precipitated from adenovirus type 12 (Ad12)-infected KB cells and Ad12-transformed hamster cells by sera of tumor-bearing hamsters and rats: Immunoprecipitates obtained with T antigen reactive sera catalyzed transfer of 32P from [γ-32P]ATP to the γ-chain of IgG. Analogous products of control cells were without significant activity. Control hamster sera precipitated no protein kinase from infected and transformed cells. Some control rat sera (syngeneic with immune sera), however, were found to precipitate protein kinase from infected and transformed cells; particularly active in this respect were sera of female breeder rats. When partially purified, highly immunoreactive T antigen preparations from transformed cells were used as a source of enzymatic activity, protein kinase was detected only in precipitates obtained with immune sera. 相似文献
962.
K. Theisen 《Journal of molecular medicine (Berlin, Germany)》1978,56(4):153-168
Zusammenfassung Tachykarde Herzrhythmusstörungen lassen sich im wesentlichen auf eine Störung der Erregungsbildung — Fokusgenese — oder der Erregungsleitung — begünstigend für eine Kreiserregung —, zurückführen. Antiarrhythmika wirken diesen beiden entscheidenden Störungen entgegen. Auf Grund ihrer Hauptwirkung auf das Aktionspotential isolierter Herzmuskelzellen in therapeutischen Dosen lassen sich die Antiarrhythmika in 4 Gruppen einteilen. Beim Menschen läßt die schwerpunktmäßige Beeinflussung der Erregungsleitung in den verschiedenen Anteilen des Erregungsleitungssystems Anwendungsschwerpunkte begründen und Nebenwirkungen voraussagen. Die Antiarrhythmikawirkung auf die elektrophysiologischen Vorgänge am kranken menschlichen Herzen sind bisher noch unzureichend untersucht, so daß für die klinische Therapie letztlich die Empirie, d.h. die systematische therapeutische Anwendung entscheidet. Für die wichtigsten Antiarrhythmika haben sich so bevorzugte Indikationen ergeben. Unter bestimmten Voraussetzungen ist in der Klinik aber auch eine pathogenetisch differenzierende Therapie möglich, wenn auf Grund der bekannten spezifischen Wirkung eines Antiarrhythmikums ein Rückschluß auf die Pathogenese möglich wird; so u.a. beim Ansprechen auf Kalziumantagonisten, Typ Verapamil, die offenbar spezifisch auf sogenannte slow response Aktionspotentiale wirken. Vorbestehende TU-Abnormitäten im EKG weisen auf eine inhomogene Repolarisation als prädisponierenden Faktor für ventrikuläre Tachykardien durch Kreiserregung hin. Beim akuten Herzinfarkt kommt es zu wechselnden elektrophysiologischen Voraussetzungen für die Entstehung von Herzrhythmusstörungen, die eine therapeutische Beeinflussung durch ein einziges Antiarrhythmikum unwahrscheinlich erscheinen lassen. In der Hospitalphase ist eine ausreichend dosierte prophylaktische Gabe von Lidokain sinnvoll, in der prähospitalen Phase ohne Überwachungsmöglichkeit jedoch von zweifelhaftem Wert. Die prophylaktische Gabe von Betarezeptorenblockern kann in der posthospitalen Nachbehandlungsphase das Risiko des plötzlichen Herztodes um 50% senken. Auch bei anderen Risikopatienten mit ventrikulären Herzrhythmusstörungen ist eine konsequente antiarrhythmische Behandlung notwendig. 相似文献
963.
Masaharu Muranaka Shuji Suzuki Kazuhiro Koizumi Hiroshi Igarashi Hiroshi Okumura Koyo Takeda Kenji Tadokoro Yoshihiko Horiuchi 《The Journal of allergy and clinical immunology》1978,62(5):276-282
All of the five commercially available benzylpenicillin preparations obtained from different sources and a PcG preparation prepared by filtration of a commercial PcG on Sephadex G10 elicited the systemic anaphylactic reactions in guinea pigs which had been immunized with benzylpenicilloyl (BPO)-Ascaris extract conjugate (BPO-As) mixed with aluminum hydroxide gel. These preparations could evoke no such reactions in guinea pigs immunized with BPO-bovine gamma globulin conjugate (BPO-BGG) emulsified with complete Freund's adjuvant. The severity of the systemic anaphylactic reactions correlated significantly with the titers of either 8-day passive cutaneous anaphylactic (8-day PCA) reactions or 4-hr PCA reactions evoked with the same benzylpenicillin preparations. In vitro benzylpenicillin preparation contracted the tracheas of the guinea pigs immunized with BPO-As. These results indicated that the commercially available benzylpenicillin preparations have enough antigenicity to evoke systemic anaphylactic reactions in guinea pigs immunized with BPO-As mixed with aluminum hydroxide gel. Such guinea pigs represent an animal model for investigation of penicillin allergy. 相似文献
964.
965.
Ribosomal binding sites on poliovirus RNA 总被引:3,自引:0,他引:3
Eucaryotic ribosome binding sites on type 1 poliovirus RNA were obtained by isolation of T1 RNase-resistant RNA fragments from 80 S ribosomes that had been bound under conditions specific for initiation of translation and prevented from translocation with sparsomycin. The fragments were analyzed by two-dimensional polyacrylamide gel electrophoresis. Three ribosome-protected (RP) oligonucleotides and several non-ribosomal-protein-protected (NP) oligonucletides were analyzed. Secondary T1 digestion of the RP fragments revealed that at least three separate species existed. By comparison of these secondary digests to T1 digests of RNaseIII fragments mapped on the polio RNA, and by electron microscopic observation of ribosomes bound to polio RNA, preferred ribosome binding sites were localized to near 115 bases from the 5′ end, just to the 3′ side of midgenome, and 780 bases from the 3′ end. 相似文献
966.
Tirthadipa Pradhan-Sundd Silvia Liu Sucha Singh Minakshi Poddar Sungjin Ko Aaron Bell Jonathan Franks Ian Huck Donna Stolz Udayan Apte Sarangarajan Ranganathan Kari Nejak-Bowen Satdarshan P. Monga 《The American journal of pathology》2021,191(5):885-901
Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Loss of β-catenin at adherens junctions is compensated by γ-catenin and dual loss of both catenins in double knockouts (DKOs) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Herein, simultaneous loss of β-catenin and γ-catenin was identified in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defects in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of transforming growth factor-β signaling and repression of hepatocyte nuclear factor 4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may play a pathogenic role in subsets of cholangiopathies. The findings also support a previously unknown role of β-catenin and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by β-catenin and γ-catenin may potentially benefit development of new therapies for cholestasis.A hallmark of epithelial cells is polarization, which is achieved by the orchestration of external cues, such as cellular contact, extracellular matrix, signal transduction, growth factors, and spatial organization.1 Hepatocytes in the liver show a unique polarity by forming several apical and basolateral poles within a cell.2 The apical poles of adjacent hepatocytes form a continuous network of bile canaliculi into which bile is secreted, whereas the basolateral membrane domain forms the sinusoidal pole, which secretes various components, such as proteins or drugs, into the blood circulation.3 Loss of hepatic polarity has been associated with several cholestatic and developmental disorders, including progressive familial intrahepatic cholestasis (PFIC) and primary sclerosing cholangitis (PSC).4,5 Although the molecular mechanisms governing hepatocyte polarity have been extensively studied in the in vitro systems, there is still a significant gap in our understanding of how polarity is established within the context of tissue during development or maintained during homeostasis.6,7 Similarly, the molecular pathways contributing to hepatic polarity are not entirely understood, and a better comprehension of hepatic polarity regulation is thus warranted.Previous studies have confirmed the role of hepatocellular junctions, such as tight and gap junctions, in the maintenance of hepatocyte polarity.8,9 Studies done in vitro and in vivo have shown that loss of junctional proteins, such as zonula occludens protein (ZO)-1, junctional adhesion molecule-A, and claudins, lead to impairment of polarity and distorted bile canaliculi formation.10, 11, 12, 13 In addition, proteins involved in tight junction assembly, such as liver kinase B1, are also involved in polarity maintenance.14 Among adherens junction proteins, various in vitro cell culture models have confirmed the role of E-cadherin in the regulation of hepatocyte polarity, possibly through its interaction with β-catenin.15,16 However, there is a lack of an in vivo model to study the role of adherens junction proteins in hepatocyte polarity and their misexpression contributing to various liver diseases.β-Catenin plays diverse functions in the liver during development, regeneration, zonation, and tumorigenesis.17, 18, 19 The relative contribution of β-catenin as part of the adherens junction is challenging to study because like in other tissues, γ-catenin compensates for the β-catenin loss in the liver.20,21 To address this redundancy, we previously reported a hepatocyte-specific -catenin and γ-catenin double-knockout (DKO) mouse model was reported.22 Simultaneous deletion of β-catenin and γ-catenin in mice livers led to cholestasis, partially through the breach of cell-cell junctions. However, more comprehensive understanding of the molecular underpinnings of the phenotype is needed.In the current study, prior preclinical findings of dual β-catenin and γ-catenin loss were extended to a subset of PFIC and PSC patients. In vivo studies using the murine model with hepatocyte-specific dual loss of β-catenin and γ-catenin showed complete loss of hepatocyte polarity compared to the wild-type controls (CONs). Loss of polarity in DKO liver was accompanied by epithelial-mesenchymal transition (EMT), activation of transforming growth factor (TGF)-β signaling, and reduced expression of hepatocyte nuclear factor 4α (HNF4α). Our findings suggest that β-catenin and γ-catenin and in turn adherens junction integrity, are critical for the maintenance of hepatocyte polarity, and any perturbations in this process can contribute to the pathogenesis of cholestatic liver disease. 相似文献
967.
A new method of detecting eye movements (EMs) during sleep is described. The method consists of an electromechanical measurement using micro-miniaturized silver cup electrodes. These electrodes, when placed on the eyelid, produce electro-oculographic (EOG) recordings similar to the usual electrical method. The eyelid method offers the advantage of a relatively “clean” recording showing only EMs and movement artifact, with no intermingling of EEG and EOG. Furthermore, the method is at least one and one half times as sensitive as the usual EOG technique. In addition to these two special advantages, it also offers the features of conventional methods, convenience of DC coupling, independence from signal converters, ease of analyzing EM directionality, and durability despite the small size of the electrodes. Fabrication of the electrodes, recording configurations, and simultaneous comparisons to both the usual EOG technique and to a strain gauge method are described. 相似文献
968.
JORGEN EKSTR
M 《Acta physiologica (Oxford, England)》1975,93(4):525-530
When the function of salivary glands was abolished by applying ligatures to their ducts and the function of one half of the diaphragm muscle was abolished by sectioning of its phrenic nerve, the choline acetyltransferase activity was found to be increased in not duct-ligated glands and in the intact hemidiaphragm 4 weeks later. The increase was not seen within the first week. The increase in activity appears to be particularly manifested in the nerve endings, since it was seen in the hemidiaphragm but not in the phrenic nerve. Increased stream of impulses in the efferent nerves is thought to be the cause of this increase in choline acetyltransferase activity. 相似文献
969.
OBJECTIVE: To examine children's competence while cycling, as demonstrated in mistakes in performance and failure to comply with safety rules. METHODS: Children in three age groups (8, 10, and 12 years) participated in a realistic yet simulated traffic environment. RESULTS: The boys' cycling speed increased steadily with age, while that of the girls increased from 8 to 10 but decreased at age 12. Most children had adequate motor control by age 10, and the youngest compensated for their less developed skills by cycling slowly and braking early at junctions. Serious mistakes, often related to the children's age and gender, consisted of the children failing to stop at signals or stopping too late, especially at short stopping range. CONCLUSIONS: There are considerable individual differences in children's cycling competence that are related to biological factors, such as age and gender, and psychological factors, such as rule compliance and choice of cycling speed. 相似文献
970.
目的 探讨力竭游泳对大鼠胃肠道 5 HT免疫反应细胞 (5 HTIR细胞 )的影响。方法 本研究以力竭游泳大鼠为运动模型 ,游泳后即刻取大鼠胃窦、十二指肠、空肠和回肠用免疫组织化学SP法检测 5 HT ,用图像分析系统测定胃肠 5 HTIR细胞数和平均灰度。结果 (1)游泳后胃窦 5 HTIR细胞数虽与对照组无明显差异 ,但阳性细胞的平均灰度却明显下降 (P <0 .0 5)。 (2 )十二指肠、空肠、回肠 5 HTIR细胞数都明显下降 ,与对照组相比有显著性差异 (P <0 .0 5) ,但只有空肠 5 HTIR细胞平均灰度明显增加 ,与对照组间有明显差异 (P <0 .0 5)。结果 胃肠道不同区域 5 HTIR细胞以不同的反应方式应答运动应激。 相似文献