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Jenny U. Johansson Nathaniel S. Woodling Qian Wang Maharshi Panchal Xibin Liang Angel Trueba-Saiz Holden D. Brown Siddhita D. Mhatre Taylor Loui Katrin I. Andreasson 《The Journal of clinical investigation》2015,125(1):350-364
Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD. 相似文献
3.
H. Nilsson J. Johansson K. Svanberg S. Svanberg G. Jori E. Reddi A. Segalla D. Gust A. L. Moore T. A. Moore 《British journal of cancer》1997,76(3):355-364
The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated. 相似文献
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Lars von Knorring Béla G. L. Almay Jan Häggendal Folke Johansson Lars Oreland Lennart Wetterberg 《European archives of psychiatry and clinical neuroscience》1986,236(3):131-138
Summary The aim of the present study was to investigate the discriminative power of a series of variables (including determination of depressive symptomatology by means of a visual analogue scale, determination of personality traits by means of the Karolinska Scales of Personality, determination of monoamine metabolites in CSF, platelet MAO activities, serum cortisol before and after dexamethasone suppression and urinary melatonin) in differentiating (a) chronic pain patients from healthy subjects, and (b) patients with idiopathic pain syndromes from patients with neurogenic pain syndromes. Separately each of the measures gave a significant but often low contribution to the discrimination, while a combination of several measures gave a complete discrimination both between healthy subjects and patients with chronic pain syndromes and between patients with idiopathic and neurogenic pain syndromes, respectively.Supported in part by grants from the Swedish Medical Research Council (grants no. 3371, 4145 and 5740) and by a grant from Stiftelsen Söderström-Königska Sjukhemmet 相似文献
6.
Michael Schenker Mikael Wiberg Simon P Kay Roland S Johansson 《Journal of plastic, reconstructive & aesthetic surgery》2007,60(1):13-23
Although toe-to-hand transfer has a defined role in the management of congenital hand deformities, it remains unclear how well children integrate the transferred digits into physiological grasping. We analysed fingertip forces in the precision grip of 13 patients when lifting a test object more than three years after free toe transfer for absent or hypoplastic digits. Clinically, most patients showed normal sensibility of transferred digits, but active motion and pinch strength were limited as compared to the normal hand. For the control of fingertip forces, two key features of the normal two-digit opposition grip were seen in all operated hands: adaptation of grip force to object weight and parallel coordination of lift and grip forces. These physiological grasping strategies developed independently of the patients' age at the time of operation, which ranged from one to 13 years. In four patients, we observed increased tangential load forces with the operated hand due to misalignments in the application of fingertips on the grasp surfaces. Such forces lead to increased grip force requirements on both fingers that may overload transferred digits with limited motor function. The need for optimal alignment of the grip axis during toe-transfer surgery is emphasised. 相似文献
7.
Identification of the site on IgG Fc for interaction with streptococci of groups A, C and G. 总被引:1,自引:1,他引:0
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The interaction between living groups A, C and G streptococci and IgG Fc was studied using human IgG, IgG Fc and IgG Fc-intermediate (Fci) fragments, chemically modified human IgG and fragment D of staphylococcal protein A (SPA). Diethylpyrocarbonate modification of His or N-acetylimidazole modification of Tyr of human IgG resulted in the loss of its capacity to inhibit the binding of radiolabelled human IgG Fc to the group A streptococci types M1 and M55, and to the group C strain SC-1, indicating that the amino acids His and Tyr are involved in the binding. Lys seems not to participate in the binding of IgG to these bacteria, however, since reductive methylation of Lys did not reduce its inhibitory capacity. Fragment D of SPA also inhibited the binding of radiolabelled human IgG Fc to strains M1, M55 and SC-1. We have previously shown that these bacteria do not bind to IgG fragments consisting of only the C gamma 2 or C gamma 3 domains. On the basis of these results, and the known relative positions in space of the His and Tyr residues on IgG Fc, it is speculated whether streptococci with IgG Fc receptors, like SPA and rheumatoid factors, interact with IgG in the interface between the C gamma 2 and C gamma 3 domains and involve His 435 and one or more of Tyr 436, His 433 and His 310. The similarities in binding sites on IgG for RFs and these bacterial Fc binding proteins suggest structural similarities between them that may be relevant to the production of rheumatoid factors in rheumatoid arthritis. 相似文献
8.
Several single agonist/antagonist primary muscle spindle afferents were simultaneously recorded in chloralose anaesthetized cats. It was shown that their dynamic and static sensitivity to sinusoidal muscle stretches could be increased or decreased via the fusimotor system by extension and flexion of the contralateral hind limb as well as by stretch of ipsilateral muscles and stimulation of ipsilateral skin nerves. The results seem to support the hypothesis that the primary muscle spindle afferents convey complex multisensory messages to the central nervous system (CNS). 相似文献
9.
Bo-Lennart Johansson Ulla Berg Ulla Freyschuss Kerstin Hall Staffan Troell 《Pediatric nephrology (Berlin, Germany)》1990,4(6):589-592
The influence of metabolic control (HbA1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients. 相似文献
10.
Gunilla Movin-Osswald Per Karlsson Margareta Hammarlund-Udenaes Lars Farde 《Psychopharmacology》1994,114(2):248-256
The D2-dopamine receptor antagonist raclopride was administered to eight healthy male subjects, who had previously experienced akathisia following antipsychotic drugs. The influence of administration rate on onset, severity and duration of akathisia and on prolactin response was studied. Raclopride 3,5 or 9 mg or placebo (P) was administered as single IV infusions during 10 min (R10 min/3 mg), 1 h (R1h/5 mg) or 4 h (R4h/9 mg) according to a randomized double-blind design. Despite a 24-fold difference in administration rate a similar peak raclopride concentration of about 350 nmol/l was obtained after all three infusions. Three of the eight subjects experienced akathisia following R10 min/3 mg and R1h/5 mg, respectively. After R4h/9 mg seven subjects experienced akathisia of longer duration but not more severe than after the short infusions. The incidence and duration of akathisia seem to be mainly related to the plasma raclopride concentrations over time, whereas the rate of administration might be more important for the severity. A maximal prolactin response was induced which was not markedly affected by the rate of administration. 相似文献