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101.
Protein kinase C is an important second messenger system, which is translocated from the cytosol to the cell membrane upon cell stimulation. We used confocal microscopy to study the spatial distribution of protein kinase C isoforms after stimulation of cultured vascular smooth muscle cells with different agonists. First, we analysed the effects of angiotensin II and platelet-derived growth factor (PDGF). Confocal microscopy showed a rapid assembly of PKC alpha along cytosolic fibres followed by a translocation towards the nucleus with angiotensin II. PDGF engendered a similar, but much slower response; however, a cytoskeletal distribution was not observed. We then investigated the effects of thrombin and bFGF on nuclear translocation. bFGF induced a rapid translocation of the isoform towards the perinuclear region and into the nucleus. bFGF had a similar effect on PKC epsilon. In contrast, thrombin had a smaller effect on nuclear translocation of PKC alpha and did not influence PKC epsilon, but instead induced a rapid nuclear translocation of PKC zeta. Thus, tyrosine kinase receptor activation via bFGF induces a rapid association of PKC alpha and epsilon within nuclear structures. Our results show that agonists cause, not only a translocation of protein kinase C isoforms into the cell membrane but also into the cell nucleus. Lastly, we analyzed the nuclear immunoreactivity of the PKC isoforms, alpha, delta, epsilon and zeta in vascular smooth muscle cells during the cell cycle. Resting cells were stimulated with foetal calf serum (FCS, 10%), which translocated PKC alpha and epsilon to the perinuclear region and into the nucleus, while PKC delta and zeta showed no increase in nuclear immunoreactivity. After 4 h of FCS, the nuclear immunoreactivity for PKC alpha and epsilon was reduced to or below control values. At 8 h, increased nuclear expression of isoforms alpha, epsilon and zeta was observed, while isoform delta was not affected. Our results demonstrate a complex spatial and temporal regulation of PKC isoforms in response to vasoactive hormones and growth factors. We suggest that protein kinase C may be important for nuclear signaling and demonstrate that nuclear translocation of PKC isoforms is differentially regulated during the cell cycle.  相似文献   
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Leptin is a hormone produced by the adipocytes to regulate food intake and energy expenditure at the hypothalamic level. It is commonly accepted that the main determinants of leptin secretion are the net amount of body fat and the mean size of adipocytes. On the contrary, important vectors of energy flux in the organism, such as food intake and energy expended on exercise, are not thought to be regulators of that secretion. To understand whether leptin is regulated by an acute energy expenditure such as strenuous exercise, 29 male athletes who had trained for marathon running were studied before and after a marathon run and compared with 22 nonobese, age-, sex-, and body mass index (BMI)-matched sedentary controls. Controls and marathon athletes showed no differences in BMI or fat-free mass. Marathon runners showed a strong reduction in total fat mass (6.2 +/- 0.4 kg; 9.1 +/- 0.5% of body fat) compared with controls (12.3 +/- 0.5 kg; 16.1 +/- 0.5% of body fat; P < 0.05). This difference in body composition was paralleled by a mean serum leptin level that in marathonians (2.9 +/- 0.2 micrograms/L) was significantly (P < 0.05) reduced compared with that in controls (5.1 +/- 0.6 micrograms/L). It is remarkable that the ratio of leptin per kg body fat, showed a very good agreement between the two groups, 0.40 +/- 0.04 microgram/L.kg for controls and 0.46 +/- 0.03 microgram/L.kg for marathonians. In the two groups, leptin was correlated with both body weight, BMI, and fat mass (P < 0.001). The marathon trajectory was the standard 42.195 km accomplished in an average time of 3 h, 17 min, 7 s, with a calculated energy expenditure of over 2800 Cal. After the marathon run, a water imbalance occurred, with a significant decrease in body weight and an increase in serum albumin. A significant (P < 0.05) reduction in leptin values was observed after the run (2.6 +/- 0.2 micrograms/L) compared with before (2.9 +/- 0.2 micrograms/L), which was more relevant considering the relative hemoconcentration. In conclusion, 1) compared with sedentary subjects, leptin levels are reduced in male marathon runners in parallel with the relevant reduction in total body fat; 2) expressed as a ratio of leptin per kg body fat, no differences were observed between marathonians and controls; and 3) after an energy expenditure of 2800 Cal in the marathon run, a reduction in leptin levels occurred. Strong changes in energy expenditure may regulate serum leptin levels in man.  相似文献   
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We discuss a patient with sarcoidosis presenting with cranial neuropathy and a cerebral mass lesion evident on imaging. Also, we review from the literature six patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the diagnostic role of Mantoux test site biopsy in patients with dominant or isolated neurologic presentation because the involved sites are not easily accessible and Kveim's test antigen is not commercially available.  相似文献   
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Of 100 patients with intermittent claudication, followed an average of six years, a surprising 78 per cent either showed improvement or remained stable regarding the presenting complaint. However, 39 per cent showed evidence of further progression of atherosclerosis. In patients with femoropopliteal occlusion in one leg, almost 40 per cent had occlusion in the one leg, almost 40 per cent had occlusion in the other leg after two to six years. The amputation rate was 7 per cent but six of these seven patients had severe diabetes. This study suggests that we are not causing limb loss by adhering to stringent criteria for bypass grafting. It also suggests that the patient with intermittent claudication without associated grave signs has a better than 50 per cent chance of improving and a better than 60 per cent chance that his disease will not show evidence of significant progression during a five to six year period. Such data should be taken into consideration when patients are considered for arterial reconstruction.  相似文献   
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The relatively good transparency of biological materials in the near infrared region of the spectrum permits sufficient photon transmission through organs in situ for the monitoring of cellular events. Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes. The copper atom associated with heme a3 did not respond to anoxia and may be reduced under normoxic conditions, whereas the heme-a copper was at least partially reducible.  相似文献   
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