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P Algenstaedt N Hennigs N Telkamp B Schwarzloh C Kausch S Matthaei N Hansen-Algenstaedt H Greten 《Hormones et métabolisme》2004,36(10):686-692
Class I alpha phosphatidylinositol (PI) 3-kinase is an important enzyme in the early insulin signaling cascade, and plays a key role in insulin-mediated glucose transport. Despite extensive investigation, the genes responsible for the development of the common forms of type 2 diabetes remain unknown. This study was performed to identify variants in the coding region of p85 alpha, the regulatory subunit of PI 3-kinase. Fibroblasts from skin biopsies from type 2 diabetics and controls were established to address this issue. P85 alpha cDNA was sequenced, and a single point mutation at codon 326 was found. This mutation resulted in a homozygous missense amino acid change Met --> Ile in one subject with type 2 diabetes and heterozygous variant in two other diabetic patients and one with severe insulin resistance. Interestingly, those patients revealed an impaired insulin-mediated insulin receptor substrate (IRS)-1 binding to p85 alpha without any alteration in IRS-2/p85 alpha association. Furthermore, IRS-1, IRS-2, p85 alpha and MAPK protein contents were not significantly changed, and neither were MAPK or Akt phosphorylation. We conclude from our data that this variant may have only minor impact on signaling events; however, in combination with variants in other genes encoding signaling proteins, this may have a functional impact on early insulin signaling. 相似文献
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The prostacyclin analogue iloprost and prostaglandin E1 suppress sterol synthesis in freshly isolated human mononuclear leukocytes 总被引:2,自引:0,他引:2
The effects of the stable prostacyclin analogue iloprost, prostaglandin E1 and prostaglandin F2 alpha on sterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a 3-fold rise in the rate of sterol synthesis from [14C]acetate or tritiated water. Iloprost and prostaglandin E1 added in increasing concentrations at zero time resulted in an inhibition of the synthesis of sterols, the suppression being 50 and 55% at a concentration of 1 mumol/1, respectively. Both prostaglandins yielded a sigmoidal log dose-effect curve. In contrast, prostaglandin F2 alpha had no influence on sterol synthesis up to a concentration of 1 mumol/1. The action of the prostacyclin analogue and prostaglandin E1 on the relative rate of sterol synthesis was not immediate, since the prostaglandins had no effect when given at 6 h to the incubation medium, and the incorporation of [14C]acetate into sterols was measured thereafter. The results suggest that prostacyclin and prostaglandin E1 affect cholesterol synthesis and therefore may play a role in the regulation of cellular cholesterol homeostasis and in the development of atherosclerosis. 相似文献
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To assess the role interleukins and mitogens play in regulating immunoglobulin (Ig) gene expression via the Ig enhancer and promoter, transgenic mice carrying two different Ig gene regulatory regions were generated. One, EkCAT, contains the Ig heavy chain enhancer (E) and the light chain promoter driving the chloramphenicol acetyltransferase (CAT) gene. In the other, EkCAT, CAT is under the control of the promoter alone. E and relative activity were assessed by CAT assay. In EkCAT mice, low CAT expression was consistently found in spleen, bone marrow, mesenteric lymph node, and thymus but not in brain, lung, or kidney. In EkCAT mice, CAT expression was detectable just above background in lymphoid tissues, suggesting a basic level of tissue specificity in the absence of the enhancer. Whole spleen cell cultures prepared from the mice were treated with lymphokines and mitogens. Lipopolysaccharide (LPS), concanavilin A (Con A), interleukin 6 (IL-6), and interferon- (IFN-) increased CAT expression to varying extents in cells derived from EkCAT mice but not in spleen cells prepared from EkCAT mice. Thus, the presence of E, in addition to the promoter, is essential for the stimulation of CAT expression mediated by these factors. B cells from EkCAT mice were separated by density into populations of small and large cells. In untreated small B cells, no CAT expression was detected and only addition of LPS resulted in an increase in CAT expression. In large B cells, CAT was expressed at a low level without addition of exogenous factors. Incubation with LPS, IL-6, Con A and IFN- caused CAT expression to increase several-fold. This transgenic system provides a means to identify exogenous factors that activate Ig enhancers and promoters.This work has been submitted in partial fulfillment of the requirements for the doctoral degree from the George Washington University. 相似文献
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Heiner Birkenbeil Manfred Eckert Prof. Dr. Manfred Gersch 《Cell and tissue research》1979,200(2):285-290
Summary Fixation of prothoracic glands of Galleria mellonella with a solution containing saponin permits immunocytochemical staining of the entire gland. By this means ecdysteroids were demonstrated electron microscopically to be present in the hyaloplasm and microtubules.Supported by Sächsische Akademie der Wissenschaften zu Leipzig 相似文献
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Summary The electron microscopical investigation of Y-organs of Astacus astacus revealed that during intermoult (stage C) the cytoplasm is poorly developed and that it increases at premoult (stage D). It then shows the typical signs of steroid production, namely agranular endoplasmic reticulum and mitochondria of the tubular type. Furthermore, a larger type of mitochondria with a regular pattern of internal structure is described.Supported by Sächsische Akademie der Wissenschaften zu LeipzigWe are grateful for technical assistance to Mrs. B. Cosack und Mrs. A. Schmidt 相似文献
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Heiner Römer 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1976,109(1):101-122
1. | The reactions of tympanic nerve fibers ofLocusta migratoria were recorded by glass microelectrodes in the metathoracic ganglion. |
2. | The units were classified by frequency-, intensity-, and directional characteristics as well as by their response pattern. The response to speciesspecific song is compared with the response to song ofEphippiger ephippiger. |
3. | The physiological properties lead to a classification into three types of low-frequency neurons (characteristic frequency 3.5–4 kHz; 4kHz; 5.5–6 kHz) and one type of high-frequency neuron (12–20 kHz). This is similar to other species (Gray, 1960, Michelsen, 1971). |
4. | Intensity-coding is done by sharp rising intensity characteristics and by different absolute thresholds of the units. |
5. | There is a marked directional sensitivity with some differences between LF and HF units. In the low frequency range the tympanal organ seems to react as a pressure gradient receiver; for high frequencies another mechanism is discussed. |
6. | No filtering of species-specific song takes place at the level of the receptor cells. |