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1.
Effects of G protein subunits from rat brain on cardiac K+ channel was examined in single atrial cells of guinea-pig, using patch clamp techniques. We found that 10 pM concentration of rat brain subunits preparation could activate the atrial muscarine receptor-gated K+ channel (IK.ACh). Neither the detergent, CHAPS, used to suspend nor the boiled preparation activated IK.ACh. Furthermore, preincubation of subunits preparation in Mg2+-free solution, which easily inactivated -GTP-S, did not affect -activation of IK.ACh. We concluded, therefore, that subunits themselves can activate IK.ACh.Supported by the grants from the Ministry of Education, Culture and Science of Japan and from the Calcium Signal Workshop on Cardiovascular Systems  相似文献   

2.
TGF- is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGF- isoforms affect TGF- production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFLF) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TGF-1, -2, or -3. Post-culture media were collected for ELISA assays of TGF-1, -2, and -3 . TGF- mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TFG-2 and -3 stimulated TGF-1 production significantly (p < 0.01 relative to control). TGF-1 stimulated TGF-2 production (p < 0.01 relative to control). TGF-3 was undetectable. Glucocorticoids significantly inhibited TGF-1 and TGF-2 production and reduced expression of the up-regulated TGF-1 and TGF-2 mRNA induced by exogenous TGF-1, -2, or -3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF--stimulated cells, it was reduced by glucocorticoids. Thus, TGF- isoforms may stimulate production of various TGF- isoforms in the lung. Glucocorticoids then may block TGF- production by modulating mRNA levels and c-Jun.  相似文献   

3.
Summary (1) The effect of active and inactive phorbol esters on synaptic transmission and on membrane properties of CA1 pyramidal cells in hippocampus have been analyzed by intracellular recording. (2) 4-phorbol-12,13 dibutyrate (PDBu), but not the -isomer, increased the firing probability, reduced the spike latency and enhanced the EPSP amplitude in response to synaptic activation. The effect was similar to the changes seen in long term potentiation. After PDBu addition it was possible to elicit further enhancement by tetanization, but not after PDBu administration. (3) A slowly developing hyperpolarization was seen after active phorbol ester application without apparent changes in the soma input resistance. (4) Active phorbol esters reduced the slow afterhyperpolarization (AHP) in these cells without affecting the intermediate AHP.  相似文献   

4.
Summary Experiments using the same glass microelectrode (6–8 M) for recording and stimulating were performed on 12 rats in which 379 cortical cells were studied in 65 penetrations through the motor and somatosensory cortical zones. To avoid anaesthetic effects the rats were chronically implanted with a head system derived from the one developed by Noda et al. (1971). These animals well accepted head fixation and the peripheral receptive fields could thus be easily investigated. In a preliminary experiment the number of pyramidal cells activated by a given stimulus intensity was evaluated. The lowest threshold intensities were always observed in the Vth pyramidal layer, as well as correspondence between cell input and output. The same type of organization, with identical thresholds, existed in the so-called Motor and Somatosensory cortical zones. Movements could be obtained when stimulating near non-PT cells (600–700 m below the cortical surface). However, thresholds were higher at this level and it is thought that the movements were due to a spread of the stimulating current to the pyramidal tract cell layer.On leave from the University of Catania  相似文献   

5.
Summary The method of one-dimensional current source density (CSD) analysis was applied to field potentials recorded from 350 m thick slices of the primary visual cortex of rats and cats. Field potentials were elicited by stimulation of the white matter and recorded along trajectories perpendicular to the cortical layers at spatial intervals of 25 to 50 m. The resulting CSD distributions resembled closely those recorded from the cat visual cortex in vivo. The responses with the shortest latency were distinct sinks in layers IV and VI probably reflecting monosynaptic EPSP's from specific thalamic afferents. From layer IV activity was relayed along three major routes: 1. to the supragranular layers via strong local connections to layer III and from there via both short and long range connections to layer II, 2. to targets within layer IV, and 3. to layer V. The source distributions suggest that the projections to layers III and II terminate on the proximal and distal segments, respectively, of apical dendrites of layer III pyramidal cells while the projection to layer V contacts the apical dendrites of layer VI pyramidal cells. These results indicate that all the excitatory pathways that are detectable with the CSD technique in the in vivo preparation remain intact in 350 m thick cortical slices. However, in the slice paired pulse stimulation did not lead to a depression of the response to the second stimulus while this is the case in vivo. This might be due to reduced inhibition in the slice which has been reported by several authors.  相似文献   

6.
The binding of human interferons to their binding site(s) was measured by the amount of radioiodinated human beta Interferon (HuIFN) displaceable by unlabeled human beta, alpha, and gamma Interferon (HuIFN, , and ). By this approach, HuIFN and HuIFN were found to interact with specific binding sites in cell membranes derived from human cells and mouse-human cell hybrids containing chromosome 21 as their only human chromosome. Specific binding was not observed with cell membranes derived from parental mouse cells or from mouse-human cell hybrids in subsequent generations that have lost human chromosome 21. Although the chromosome 21-positive mouse-human cell hybrids are sensitive to the antiviral effects of HuIFN and HuIFN, they are found to be insensitive to the antiviral effect of HuIFN and to lack specific HuIFN binding sites. These results suggest that the HuIFN and HuIFN but not HuIFN binding sites are coded for by genes located on chromosome 21. The lack of a chromosome 21 gene dosage effect on the inducibility of the antiviral state by HuIFN is consistent with this hypothesis.  相似文献   

7.
Summary Five corticotropin-producing tumours were examined for peptides related to the corticotropin--lipotropin precursor. Two were basophil pituitary adenomas and three were bronchial carcinoids. The cells of the two pituitary adenomas stained with antisera against -endorphin and against pro--melanotropin, the NH2-terminal fragment of the corticotropin--lipotropin precursor, but not with antisera against -melanotropin or -lipotropin. The corticotropin-storing tumor cells of the bronchial carcinoids stained with antisera against -endorphin, -lipotropin or pro--melanotropin. Only one of the three bronchial carcinoids contained cells reacting with the antiserum against -melanotropin. Although the two types of corticotropin-storing tumours (pituitary adenoma and bronchial carcinoid) differed with respect to -lipotropin content, the over-all picture indicates that the proteolytic processing of the corticotropin precursor proceeds along similar lines in tumour cells and in pituitary corticotrophs.An acetic acid extract of one of the bronchial tumours was subjected to gel chromatography and immunochemical analysis of material related to pro--melanotropin. The immunoreactive material displayed a considerable size heterogeneity, with the predominant components having a molecular weight larger than that of authentic pro--melanotropin.  相似文献   

8.
The purpose of the present study was to investigate the involvement of cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human periodontal ligament (PDL) fibroblasts stimulated with a proinflammatory cytokine, inerleukin-1 (IL-1), and to examine the effect of interleukin-4 (IL-4), a Th2 cytokine, and interferon- (IFN-), a Th1 cytokine, on PG production by the cells. IL-1-stimulated PDL fibroblasts produced prostaglandin E2 (PGE2) in a time-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor, completely inhibited PGE2 production by IL-1-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detected in IL-1-stimulated PDL cells, although not detected in unstimulated cells, while expression of COX-1 mRNA was in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA expression, COX activity and PGE2 production in IL-1-stimulated cells. IL-4 and IFN- suppressed PGE2 production by IL-1-stimulated PDL fibroblasts, but COX activity enhanced by IL-1 treatment was significantly inhibited by IL-4, not by IFN-. Northern blot analysis showed that IL-4 depressed COX-2 mRNA expression with no effect on COX-1 mRNA expression. On the other hand, IFN- had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2 is primarily responsible for PGE2 production by IL-1-stimulated human PDL fibroblasts and that IL-4 inhibited PGE2 production by IL-1-stimulated PDL fibroblasts through down-regulation of COX-2 expression, while IFN- suppressed the PGE2 production with no effect on COX-2 expression.  相似文献   

9.
We attempted to estimate in living adherent epithelial alveolar cells, the degree of structural and mechanical heterogeneity by considering two individualized cytoskeleton components, i.e., a submembranous cortical cytoskeleton and a deep cytoskeleton (CSK). F-actin structure characterizing each CSK component was visualized from spatial reconstructions at low and high density, respectively, especially in a 10-m-cubic neighborhood including the bead. Specific mechanical properties (Young elastic and viscous modulus E and ) were revealed after partitioning the magnetic twisting cytometry response using a double viscoelastic solid model with asymmetric plastic relaxation. Results show that the cortical CSK response is a faster ( 1 0.7s), softer (E1: 63-109 Pa), moderately viscous (1: 7-18 Pa s), slightly tensed, and easily damaged structure compared to the deep CSK structure which appears slower (2 min), stiffer (E2: 95-204 Pa), highly viscous (2: 760-1967 Pa s), more tensed, and fully elastic, while exhibiting a larger stress hardening behavior. Adding drug depolymerizing actin filaments decreased predominantly the deep CSK stiffness. By contrast, an agent altering cell–matrix interactions affected essentially the cortical CSK stiffness. We concluded that partitioning the CSK within cortical and deep structures is largely consistent with their respective functional activities. © 2003 Biomedical Engineering Society. PAC2003: 8716Ka, 8716Ac, 8380Lz  相似文献   

10.
The membrane electrical parameters and component conductances of rat extensor digitorum longus muscle fibres were studied in vitro at 30 °C with standard two microelectrode square pulse cable analysis in the presence of protein kinase C (PKC) activators and inhibitors. The PKC activator, 4--phorbol-12,13 dibutyrate (4--PDB), (2–90nM) blocked up to 67% chloride conductance (G Cl) in rat skeletal muscle fibres and induced myotonic hyperexcitability. The concentration necessary to produce a 50% block of the membrane G Cl was 23 nM. The inactive 4--phorbol-12,13 dibutyrate had no effect at 2 M. The blocking effect of 4--PDB on G Cl was prevented by preincubation of the preparations with the PKC inhibitors, staurosporine (1–5 M) and tetrahydropapaverolone (50–100 M). The blocking effects on membrane G Cl of 4--PDB and its antagonism by the inhibitors used support the concept of the involvement of PKC in regulating Cl channels of mammalian skeletal muscle fibres.  相似文献   

11.
Developmental cell death: morphological diversity and multiple mechanisms   总被引:43,自引:0,他引:43  
Summary Physiological cell death is a widespread phenomenon in the development of both vertebrates and invertebrates. This review concentrates on an aspect of developmental cell death that has tended to be neglected, the manner in which the cells are dismantled. It is emphasized that the dying cells may adopt one of at least three different morphological types: apoptotic, autophagic, and non-lysosomal vesiculate. These probably reflect a corresponding multiplicity of intracellular events. In particular, the destruction of the cytoplasm in these three types appears to be achieved primarily by heterophagy, by autophagy and by non-lysosomal degradation, respectively. The various mechanisms underlying both nuclear and cytoplasmic destruction are reviewed in detail. The multiplicity of destructive mechanisms needs to be born in mind in studies of other aspects of cell death such as the signals which trigger it, since different signals probably trigger different types of cell death.  相似文献   

12.
Résumé Localisé de part et d'autre du labyrinthe, le paraplacenta ou bordure brune, est constitué de la membrane allanto-chorionique faisant face à l'épithélium utérin. Les cellules chorioniques phagocytent et dégradent des hématies d'origine maternelle; cette activité est probablement cyclique. Durant la phase d'ingestion, l'hématie est phagocytée à l'apex de la cellule, puis après fusion de lysosomes avec la vacuole phagocytique, la phase digestive commence et se déroule principalement dans la zone médiane de la cellule, au niveau de vacuoles de tailles plus réduites. Certaines vacuoles contiennent des figures myéliniques associèes ou non à des granules de taille variable, d'autres un matériel finement granulaire. La brève phase d'élimination se caractérise par la présence au voisinage de la lamelle basale et des capillaires foetaux, de corpuscules de 1,000 Å probablement constitués d'agrégats de particules de ferritine. Ces corpuscules exhibent une activité pseudoperoxydasique. Cette érythrophagocytose placentaire représente la source principale de fer pour le foetus.Les microvilli, les vésicules de micropinocytose, le système tubulaire et les corps multivésiculaires de la zone apicale de la cellule, suggèrent une fonction d'absorption de protéines de la cellule. Il en est de même de la richesse du cell coat de la surface membranaire apicale.
Summary Located on all sides of the placental labyrinth, the paraplacenta or brown border is constituted by the chorioallantoic membrane and the uterine mucosa facing it. The chorionic cells are actively engaged in the uptake and subsequent breakdown of extravased maternal erythrocytes.This phagocytic activity is probably cyclic in nature. In the ingestion phase an erythrocyte is phagocytosed in the apex of a chorionic cell, and the digestive phase occurs after fusion of lysosomes with the phagocytic vacuole. Subsequent breakdown of the red cell membrane leads to release of the content of the erythrocyte into the vacuole. Then the breakdown proceeds in smaller vacuoles of the median zone of the cell. Some vacuoles contain concentric whorls of membrane, associated with granules of variable size; others contain a finely granular material. The short-lived final, or elimination, phase is characterized by the presence of 1,000 Å finely granular bodies along the basement membrane and in close approximation to fetal capillaries. These non-membrane-bound bodies seem to be constituted of ferritinlike particles and exhibit pseudoperoxydasic activities with D.A.B. procedures. This paraplacental erythrophagocytosis is the major source of iron for the fetus.At their apical surface, the chorionic cells exhibit microvilli, micropinocytotic vesicles and a well-defined cell coat. The underlying cytoplasm contains numerous absorption vesicles or tubules and multivesicular bodies suggestive of protein absorption.
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13.
The expression of the 1 integrins was examined immunohistochemically in synoviocytes from normal synovial membrane and from chronic synovitis of different aetiology and intensity. Normal synoviocytes were 61-positive but lacked 1 through 5. In mild inflammation type A synoviocytes neo-expressed 1, 3, and 5 chains. In severe inflammation both type A and B synoviocytes expressed 3, 4, 5, and 6 chains. The effects of inflammatory cytokines, as single agents or in combination, on the 1 integrin expression in cultured normal synoviocytes was determined by immunocytochemistry and flow cytometry. The 1 chain, while absent in unstimulated synoviocytes, was induced by interleukin-1 (IL-1), tumour necrosis factor- (TNF-), and interferon- (INF-). This effect was enhanced by combining IL-1 and TNF-. Expression of the 3 chain was up-regulated by IL-1 and, more intensely, by IFN-. Transforming growth factor (TGF-) inhibited the up-regulating effect of IL-1 and antagonized the effect of IFN- on 3 chain expression. Expression of the 5 chain was up-regulated significantly by co-stimulation through IL-1 together with TGF- or TNF-. Thus, the 1 integrin profile of cytokine activated synoviocytes in vitro resembled that of synoviocytes in synovitis in situ. These data suggest that IL-1, TNF-, IFN-, and TGF- are likely to be among the effectors regulating 1 integrin expression in synoviocytes in vivo.  相似文献   

14.
Endothelial cells play an important role in adhesive interactions between circulating cells and extracellular matrix proteins. In vitro studies have shown that many of these processes are mediated by a superfamily of heterodimeric transmembrane glycoproteins called integrins. The distribution patterns of 1, 3 and 4 integrin subunits in endothelial cells (EC) in situ were examined immunohistochemically on serial forzen sections of a wide range of non-neoplastic tissues and of vascular tumours, both benign and malignant. Expression of the 1 subunit was a constitutive feature of EC. Among the 1-associated subunits, 5 and 6 were broadly distributed in EC, irrespective of vessel size and microenvironment. The 3 subunit displayed intermediate levels of expression with a slight preference for small vessel EC. Presence of 1 was confined to EC of capillaries and venules/small veins. Expression of 2 in EC was inconsistent. With rare exceptions, the 4 chain was absent in EC. The 3 and v subunits were expressed in most EC, though not always concomitantly. In contrast to the 1 chain, however, these integrin subunits were absent in EC of glomerular capillaries and were expressed variably in sinusoidal EC. The 4 chain was evenly present in the great majority of EC, except for those of large vessels. In vascular tumours, the patterns of 1 and 1 to 6 subunit expression generally corresponded to those found in their non-neoplastic counterparts. Expression of 3, v and 4 chains, however, decreased in neoplasia, especially in angiosarcomas. These data show that EC dispose of broad and at the same time differential repertoires of integrin subunits that presumably reflect vessel-type associated functional differences among these cells. In vascular tumours, the orthologous distribution patterns of 1 and 1 to 6 chains are conserved in most instances while the amounts of 3, v and 4 subunits expressed in EC tend to decrease in the course of malignant transformation.Dedicated to Prof. Dr. med. Dres. h.c. Wilhelm Doerr on the occasion of his 80th birthday  相似文献   

15.
We report on a patient with a rare hepatosplenic T-cell lymphoma ( TCL) presenting clinically with B-symptoms, hepatosplenomegaly and pancytopenia. During the initial stage of the disease the sparse malignant cells could not be detected histologically. Furthermore, their identification was obscured by massive macrophage proliferation with haemophagocytosis in the spleen. Diagnosis was established by detection of a clonal T-cell receptor (TcR) rearrangement and, retrospectively, by demonstration of rare cells expressing an aberrant T-cell phenotype. The findings in this patient emphasize that minimal neoplastic T-cell infiltrates can lead to severe clinical symptoms. Initial biopsy findings may be misinterpreted as benign. TCL may elaborate lymphokines that suppress haematopoiesis, leading to pancytopenia and macrophage proliferation.  相似文献   

16.
-Catenin has emerged as an important component of the adherens junctions between epithelial cells. As a result of studies of its interaction with theAPC gene product, it has been implicated in the development of colorectal cancer. -Catenin, -catenin, E-cadherin and APC appear to mediate contact inhibition in epithelia. As part of the study of the organization of the -catenin gene, we have isolated yeast artificial chromosomes (YACs) to characterize its intron/exon structure. YAC fluorescencein situ hybridization analysis and polymerase chain reaction analysis of somatic cell hybrid DNAs show that -catenin maps in the 3p21–22 region, the location of tumour-suppressor genes deleted in small-cell lung cancer (SCLC) and other disorders. -Catenin YACs will provide a source of microsatellite markers useful in loss of heterozygosity studies to assess the importance of -catenin deletions in SCLC.  相似文献   

17.
Zusammenfassung Die farbvalenzmetrische Untersuchung von 34 Diabetikerschädeln ergab beim Vergleich mit 56 Kontrollfällen den gleichen Farbton und die gleiche spektrale Sättigung. Bei den Schädeln der Diabetiker ließ sich jedoch eine verminderte Helligkeit nachweisen. Die Farbänderung ist daher für eine Vermutungs-diagnose Diabetes mellitus mit Recht zu verwenden. Es wird jedoch vorgeschlagen, nicht mehr von einer Gelbfärbung, sondern von einer Dunklerfärbung zu sprechen. Das Ausmaß der dunkleren Färbung ist eindeutig positiv zur Krankheitsdauer korreliert. Frühestens nach 6 Jahre bestehendem Diabetes ist eine signifikante Farbänderung zu erwarten. Die Ursache dieser Farbänderung ist unbekannt. In Modellversuchen mit ikterischen Schädeln konnte gezeigt werden, daß die farbmetrischen Kurven bei in vivo entstandenem Ikterus und bei künstlich durch Gallenflüssigkeit erzeugter Verfärbung prinzipiell gleich verlaufen.
Reflex photometric studies of the yellow discoloration of the calvaria in diabetes mellitus
Summary The shade of color and the spectral saturation of the calvariae of 34 diabetic patients were the same colorimetrically as those of 56 control cases. The calvariae of the diabetics showed, however, a reduced brightness. Consequently, the color change may rightfully be used for the presumptive diagnosis of diabetes mellitus. It is suggested, however, that one should not refer anymore to a yellow discoloration, but instead to a darker discoloration. The degree of the darker color is clearly correlated directly with the duration of illness. The earliest a significant color change may be expected is after six years of diabetes. The cause of the color change is unknown. In model experiments it could be shown, that the colorimetric curves of calvariae discolored by icterus during life are principally the same as the curves of calvariae discolored artificially with bile.
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18.
Zusammenfassung Es wird über 2 Patienten berichtet, die als Ehepartner mit einer zeitlichen Differenz von etwa 2 Monaten die durch das Virus Marburg hervorgerufene Infektionskrankheit durchmachten. Die Ehefrau zeigte 4 Tage nach einem Coitus die ersten Symptome. Bei dem Ehemann fand sich zur selben Zeit im Ejaculat ein Erregerantigen, das im Meerschweinchentest, durch Immunfluoreszenz und im Phasenkontrast nachgewiesen werden konnte. Aufgrund dieser Befunde muß eine spermatogene Übertragung des Virus Marburg angenommen werden.
Summary A patient who had suffered from Virus Marburg infection had intercourse with his wife two months after dismissal from hospital. Four days after exposure his wife developed symptoms and signs of this disease. The infectionsness of the sperm could be shown by transmission to the guinea pig and by demonstration of virus antigen in the husband's sperm by phase contrast and immune fluorescence techniques. These findings strongly suggest a spermatogenous infection of Virus Marburg.
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19.
Summary The length and distribution of Schwann cells along fibres in the ventral root L7 of the developing cat have been studied electron microscopically in serial sections. The average Schwann cell length at the beginning of myelin formation — the initial internodal length — was 118 m (110 m in -axons and 124 m in -axons). The number of Schwann cells found in a fully developed root segment was already present at the beginning of the myelination. It showed no systematic age-dependent variation from the beginning of myelination to adulthood. The Schwann cells associated with -axons increased their length 12.6 times during this period, while the root elongated 5.6 times. About 50% of the Schwann cells had to be eliminated in order to make the elongation of the remaining Schwann cells possible. Corresponding calculations from the mean length of Schwann cells associated with -axons, showed that about 50% too few Schwann cells were associated with the -axons during the period of initial myelination of the -axons. At birth, when the myelination of -axons had just begun, both the large surplus along -axons and the deficit along -axons had disappeared. We suggest that Schwann cells are eliminated from the -axons and re-utilized along the -axons. During this process of cellular redistribution, affected cells constitute so-called aberrant Schwann cells.  相似文献   

20.
Summary The nerve supply to 25 poles of muscle spindles in the monkey was reconstructed by light microscopy of serial 1-m thick transverse sections of lumbrical muscles. Twenty of 60 motor axons that supplied the spindle poles were identified as skeletofusimotor (). Twenty-eight percent of the spindle poles were innervated by axons, in addition to axons. Every -innervated spindle pole transected an endplate zone of extrafusal muscle. Most axons coinnervated extrafusal fibers rich in mitochondria and the nuclear bag1 or nuclear chain intrafusal fibers. All but two axons innervated one type of intrafusal fiber only. The intramuscular organization of motor system in lumbrical muscles of the monkey was similar to that of the cat tenuissimus muscle. The function of -innervated spindles may be preferentially to monitor mechanical disturbances arising from the activity of extrafusal muscle units with which they share motor innervation.  相似文献   

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