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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
61.
Chiara Fenoglio Daniela Galimberti Laura Piccio Diego Scalabrini Paola Panina Cecilia Buonsanti Eliana Venturelli Carlo Lovati Gianluigi Forloni Claudio Mariani Nereo Bresolin Elio Scarpini 《Neuroscience letters》2007
Triggering Receptor Expressed on Myeloid cells (TREM)2 deficiency originates a genetic syndrome characterized by bone cysts and presenile dementia, named Nasu-Hakola disease (NHD). Early onset dementia and marked involvement of frontal regions are features characterizing both NHD and other kinds of neurodegenerative disorders, such as Frontotemporal Lobar Degeneration (FTLD), and, in some cases, Alzheimer's disease (AD). Three Single Nucleotide Polymorphisms (SNPs) in TREM2 coding region were screened by allelic discrimination in a population of probable AD patients as well as FTLD patients as compared with age-matched controls. In addition, mutation scanning of the coding region of TREM2 gene was carried out in 7 patients with early onset AD (EOAD), 16 FTLD, and 20 controls. None of the SNPs analyzed was present, either in patients or controls. Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms. These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes. 相似文献
62.
What evidence is there for the existence of individual genes with antagonistic pleiotropic effects? 总被引:6,自引:0,他引:6
Leroi AM Bartke A De Benedictis G Franceschi C Gartner A Gonos ES Gonos E Fedei ME Feder ME Kivisild T Lee S Kartaf-Ozer N Kartal-Ozer N Schumacher M Sikora E Slagboom E Tatar M Yashin AI Vijg J Zwaan B 《Mechanisms of ageing and development》2005,126(3):421-429
Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems--although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study. 相似文献
63.
Vegetarians may have subtle nutritional deficiencies which have been related to the occurrence of an unrecognized malabsorption syndrome. The excess phytate content in cereals, nuts, legumes and oilseeds which represent the mainstay of their food intake, seems to play a central role in the pathogenesis of this malabsorption syndrome as an inverse relationship has been shown to link the phytate content of the diet with the intestinal absorption of trace minerals and proteins. We postulate that manipulating the endogenous digestive microflora of subjects on a vegetarian diet through administering probiotic lactic bacteria would represent an innovative tool to counteract the occurrence of the malabsorption syndrome dependent on the high phytate content of their diet. Even though there are no data about the composition of endogenous digestive microflora in subjects on a vegetarian diet, we expect that probiotic lactobacilli can interact with or affect distinct yet interrelated components within the intestinal milieu, such as epithelial cells, enteric flora, and/or mucosal immune cells. This would ultimately translate into the correction of the unregulated mechanisms implicated in the altered intestinal absorption of trace metals and proteins commonly seen in vegetarians. Clinical experience with probiotic therapy of patients with inflammatory bowel disease fully agrees with this view. One additional point of interest is that probiotic lactobacilli, and other species of the endogenous digestive microflora as well, are an important source of the enzyme phytase which catalyses the release of phosphate from phytate and hydrolyses the complexes formed by phytate and metal ions or other cations, rendering them more soluble ultimately improving and facilitating their intestinal absorption. The regular intake of probiotic preparation, may represent a cheap and safe tool in order to convert a diet with a low potential for bioavailability of trace minerals and proteins, such as the vegetarian diet, into a diet with a high bioavailability potential. The benefit of such an approach would not be restricted to vegetarians. 相似文献
64.
Macchi C Popolizio A Casamorata F Bicchi S Pieroni A Molino Lova R Miniati B Gulisano M Catini C Conti AA Gensini GF 《Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia》2002,107(2):93-97
Fifty-four subjects, aged between 20 and 35 years, divided into two subgroups, respectively 30 healthy subjects (17 males and 13 females) and 24 subjects with "gonalgia sine materia" (13 males and 11 females) underwent isokinetic exercise test in order to compare their dominant limb with the not dominant one as regard as the strength of extensor and flexor muscles of the knee. No statistically significant difference was found in any of the studied parameters in the comparison between the dominant limb and the not dominant one, both within the subgroup of healthy subjects and within the subgroup of subjects with "gonalgia sine materia". Authors conclude that psychological features may play a preeminent role in the genesis, as well as in the maintenance of "gonalgia sine materia", thus confirming previous data available in medical literature. 相似文献
65.
Simona Di Terlizzi Elisabetta Zino Benedetta Mazzi Chiara Magnani Cristina Tresoldi Serena Kimi Perna Marco Bregni Silvano Rossini Fabio Ciceri Claudio Bordignon Chiara Bonini Katharina Fleischhauer 《Biology of blood and marrow transplantation》2006,12(1):95-101
Minor histocompatibility antigens (mHags) HA-1 and HA-2 are encoded by biallelic loci, with immunogenic variants, HA-1H and HA-2V, which induce strong HLA-A2-restricted alloreactive T-cell responses, and nonimmunogenic counterparts, HA-1R and HA-2M, which represent functional null alleles that are poorly presented by HLA class I molecules. HA-1 and HA-2 are potential targets of selective graft-versus-leukemia and graft-versus-tumor reactivity after allogeneic hematopoietic stem cell transplantation (HSCT); however, these applications are restricted to a limited number of patients. Here, we show that a far more frequent application of HA-1 and HA-2 disparity relies on their use as markers for the state of host chimerism after allogeneic HSCT. We have determined allelic frequencies of 29.3% and 70.7% for HA-1H and HA-1R, respectively, and of 83.7% and 16.3% for HA-2V and HA-2M, respectively, in >200 healthy individuals from northern Italy. Similar frequencies were observed in nearly 100 patients affected by hematologic malignancies or solid tumors, thus showing that HA-1 and HA-2 variability are not associated with the presence of cancer. On the basis of these data, we predict that HA-1 and HA-2 can be used in 32.8% and 23.5% of Italian transplant patients, respectively, as markers for the state of host chimerism, whereas exploitation of disparity for these mHags for targeted immunotherapy will be possible in 10.7% and 1.1% of Italian patients, respectively. Retrospective HA-2 typing of bone marrow aspirates obtained from a patient during complete remission or recurrence of acute myeloid leukemia after haploidentical HSCT showed the feasibility of using HA-2 as a surrogate marker for disease monitoring. Because of an apparent north-south gradient for HA-1 allelic frequencies, with higher frequencies for the HA-1H variant reported in white populations from Southern Europe as compared with Northern Europe and North America, the diagnostic applicability of HA-1 disparity will be slightly more frequent in transplant patients from the north. Taken together, our data show that determination of HA-1 and HA-2 variability can be an important parameter for the selection of allogeneic stem cell donors, in particular for patients affected by hematologic malignancies without a tumor-specific molecular marker. 相似文献
66.
Paolo Cerretelli Bruno Grassi Lei Xi Federico Schena Claudio Marconi Michael Meyer Guido Ferretti 《European journal of applied physiology》1995,71(4):287-294
To gain an insight into the origin of the phase I ventilatory response to exercise (ph I) in humans, pulmonary ventilation WE) and end-tidal partial pressures of oxygen and carbon dioxide (P
ETO2 and P
ETCO2, respectively) were measured breath-by-breath in six male subjects during constant-intensity exercise on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output (Q2) was also determined beat-by-beat by impedance cardiography on eight subjects during moderate exercise (50 W), and the C02 flow to the lungs (Q2·CvCO2 where CvCO2 is concentration of CO2 in mixed veneous blood) was estimated with a time resolution of one breathing cycle. In N, the initial abrupt increase of PE during ph I (VE approximately 18 l · min–1 above rest) was followed by a transient fall. When P
ETCO2 started to increase (and P
ETO2 decreased) VE increased again (phase II ventilatory response, ph II). In H, during ph I VE was similar to that of N. By contrast, during ph II VE kept gradually decreasing and started to increase only when P
ETCO2 had returned to approximately 40 mmHg (5.3 kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal shift of the time-course of VE during ph II became apparent. No correlation was found between C02 flow to the lungs and VE during ph I. These results are interpreted as suggesting that an increased C02 flow to the lungs does not constitute an important factor for the initial hyperventilatory response to exercise. They are rather compatible with a neural origin of ph I, and would support the neurohumoral theory of ventilatory control during exercise. 相似文献
67.
68.
Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients. 总被引:2,自引:0,他引:2
Davide Treré Claudio Ceccarelli Mario Migaldi Donatella Santini Mario Taffurelli Elena Tosti Pasquale Chieco Massimo Derenzini 《Applied immunohistochemistry & molecular morphology》2006,14(3):314-323
The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments. 相似文献
69.
Dendritic cells (DC) and natural killer (NK) cells, the main cellular components of the innate immune system, participate
in the most ancient first line of defense against infections. Both types of cells patrol peripheral tissues, whereas their
rapid recruitment and activation at mucosal surfaces [the major entry point for the human immunodeficiency virus (HIV)] is
a hallmark of acute inflammatory response. The ability of HIV to survive and replicate in the human host relies upon several
molecular mechanisms eluding the immune surveillance of both adaptive immunity and of DC and NK cells beginning with the acute
phase of primary HIV infection. DC and NK cells, unlike CD4+ T cells, are impaired more functionally rather than being depleted by HIV infection.
In this article we will review some of the aspects of DC/NK cells interaction with HIV infection both in vitro and in vivo,
and we will also speculate on the potential consequence for HIV pathogenesis and for the capacity of the virus to escape the
surveillance of the innate immune system. 相似文献
70.
Claudio Marconi Mauro Marzorati Daniele Sciuto Alessandra Ferri Paolo Cerretelli 《The Journal of physiology》2005,569(2):667-675
High-altitude Tibetans undergo a pattern of adaptations to chronic hypoxia characterized, among others, by a more efficient aerobic performance compared with acclimatized lowlanders. To test whether such changes may persist upon descent to moderate altitude, oxygen uptake of 17 male Tibetan natives lifelong residents at 3500–4500 m was assessed within 1 month upon migration to 1300 m. Exercise protocols were: 5 min treadmill walking at 6 km h−1 on increasing inclines from +5 to +15% and 5 min running at 10 km h−1 on a +5% grade. The data (mean ± s.e.m. ) were compared with those obtained on Nepali lowlanders. When walking on +10, +12.5 and +15% inclines, net of Tibetans was 25.2 ± 0.7, 29.1 ± 1.1 and 31.3 ± 0.9 ml kg−1 min−1 , respectively, i.e. 8, 10 and 13% less ( P < 0.05) than that of Nepali. At the end of the heaviest load, blood lactate concentration was lower in Tibetans than in Nepali (6.0 ± 0.9 versus 8.9 ± 0.6 m m ; P < 0.05) . During running, of Tibetans was 35.1 ± 0.8 versus 39.3 ± 0.7 ml kg−1 min−1 (i.e. 11% less; P < 0.01). In conclusion, during submaximal walking and running at 1300 m, Tibetans are still characterized by lower aerobic energy expenditure than control subjects that is not accounted for by differences in mechanical power output and/or compensated for by anaerobic glycolysis. These findings indicate that chronic hypoxia induces metabolic adaptations whose underlying mechanisms still need to be elucidated, that persist for at least 1 month upon descent to moderate altitude. 相似文献