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61.
We have shown that brief exposure to amphetamine leads to sustained glutamate-dependent increases in expression of the neurotrophic, neuroprotective factor, basic fibroblast growth factor, in astrocytes in dopaminergic cell body regions and that blockade of basic fibroblast growth factor in this region prevents the development of behavioral sensitization to amphetamine. Here we examine the effects of prolonged exposure to an escalating-dose regimen of amphetamine known to induce long-lasting sensitization to amphetamine and leading to increases in neuronal dendritic length and spine density in nucleus accumbens and prefrontal cortex and to decreases in spine density in occipital cortex. Astrocytic basic fibroblast growth factor immunoreactivity was increased in both dopaminergic cell body and terminal regions one week after termination of a two-week amphetamine treatment (1-4mg/kg). These effects were not evident one week after a five-week treatment (1-9mg/kg) and, in fact, one month later basic fibroblast growth factor levels in cell body regions were decreased. In the occipital cortex, basic fibroblast growth factor immunoreactivity was decreased one week after the two-week amphetamine treatment, but was not different from that seen in saline-treated animals after the five-week treatment. Increased astrocytic basic fibroblast growth factor expression appears to be an early, but relatively prolonged, response to amphetamine exposure and seems to parallel structural changes induced by repeated drug exposure.These findings suggest that basic fibroblast growth factor may participate in the development of structural changes brought about by amphetamine. The fact that the basic fibroblast growth factor response is not maintained after prolonged intense exposure to amphetamine suggests that the factors that initially induce basic fibroblast growth factor expression are self-regulating. 相似文献
62.
Y Chromosome and Mitochondrial DNA Characterization of Pasiegos, a Human Isolate from Cantabria (Spain) 总被引:3,自引:3,他引:3
N. Maca-Meyer P. Sánchez-Velasco C. Flores J.-M. Larruga A.-M. González A. Oterino F. Leyva-Cobián 《Annals of human genetics》2003,67(4):329-339
Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non‐Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E‐M81) with North African assignation, and Y chromosomal (R‐SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre‐V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south‐western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization. 相似文献
63.
Trinidad Hernandez-Caselles Gonzalo Rubio Miguel R. Campanero Miguel Angel del Pozo M. Muro Francisco Sanchez-Madrid Pedro Aparicio 《European journal of immunology》1993,23(11):2799-2806
Optimal activation of human T cells mediated by ligation of CD3/T cell receptor (TcR) complex requires co-stimulatory signals. These can be provided by the adhesive interaction between receptor molecules on T cells and their counter-receptors on antigen-presenting cells. Soluble ICAM-3, anti-ICAM-3 and anti-CD3 mAb were utilized to address the role of the ICAM-3/LFA-1 pathway in TcR/CD3-dependent or -independent T cell activation. Immunoaffinity-purified ICAM-3 co-immobilized with suboptimal concentrations of anti-CD3 monoclonal antibody (mAb) stimulated T lymphocytes as monitored by the expression of the lymphocyte activation antigens CD25 and CD69. The mechanism underlaying this activation appear to involve the interaction of ICAM-3 with a β2 integrin, likely to be LFA-1, since mAb to the CD18 chain completely inhibited T cell activation. Similar experiments demonstrated that anti-ICAM-3 mAb were able to co-stimulate both resting (cord blood) and activated (T cell clones) T lymphocytes. On the contrary, anti-ICAM-1 mAb were only co-stimulatory for CD25 expression on activated but not on resting T cells. In addition, we have found that some γδ T cell clones bearing the Vδ1 segment were activated by direct mAb engagement of ICAM-3 in the absence of TcR/CD3 occupancy. Furthermore, immobilized anti-ICAM-3 mAb also induced development of dentritic processes. In conclusion, our data suggest that ICAM-3 on the surface of both T cells and antigen-presenting cells plays an essential role in the initiation of the immune response. 相似文献
64.
Xiaoyu Wang Mingzhen Zhang Regina R. Woloshun Yang Yu Jennifer K. Lee Shireen R. L. Flores Didier Merlin James F. Collins 《Nutrients》2021,13(5)
Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including 59Fe (as FeCl3) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH. 相似文献
65.
66.
Daniel López-Padilla Francisco García-Río Adolfo Alonso-Arroyo Nuria Arenas Valls Alicia Cerezo Lajas Marta Corral Blanco Virginia Gallo González Milagros Llanos Flores María Martínez Redondo Natalia Martos Gisbert Elena Ojeda Castillejo Marta Padilla Bernáldez Marta Pérez Gallán Vania Prudencio Ribera Luis Puente Maestu Beatriz Recio Moreno Elena Rodríguez Jimeno Ana Sánchez Azofra José Ignacio de Granda-Orive 《Archivos de bronconeumologia》2021,57(2):146-147
67.
David P. Al-Adra Laura Hammel John Roberts E. Steve Woodle Deborah Levine Didier Mandelbrot Elizabeth Verna Jayme Locke Jonathan D'Cunha Maryjane Farr Deirdre Sawinski Piyush K. Agarwal Jennifer Plichta Sandhya Pruthi Deborah Farr Richard Carvajal John Walker Fiona Zwald Thomas Habermann Morie Gertz Philip Bierman Don S. Dizon Carrie Langstraat Talal Al-Qaoud Scott Eggener John P. Richgels George J. Chang Cristina Geltzeiler Gonzalo Sapisochin Rocco Ricciardi Alexander S. Krupnick Cassie Kennedy Nisha Mohindra David P. Foley Kymberly D. Watt 《American journal of transplantation》2021,21(2):460-474
Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy. 相似文献
68.
Hillarey K. Stone Katherine VandenHeuvel Alexander Bondoc Francisco X. Flores David K. Hooper Charles D. Varnell Jr 《American journal of transplantation》2021,21(12):4061-4067
Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes. 相似文献
69.
Gonzalo Domínguez Eladio Cardiel Elsa Snchez Pablo-Rogelio Hernndez 《Journal of radiation research》2021,62(2):259
To assess the effects of exposure to extremely low-frequency magnetic fields (ELF-MFs) on MDCK cell lines, experiments were performed in a chamber under controlled conditions (temperature, humidity and CO2). Therefore, the measured physicochemical and electrical changes in the cells are due solely to the magnetic field exposure and not to external factors. A developed sinusoidal magnetic field generator produced the ELF-MFs with a uniform magnetic field and adjustable intensity and frequency. Three experimental indicators were used: (i) transepithelial electrical impedance (TEEI); (ii) cell migration and proliferation; and (iii) expression of the proteins of the tight junctions, and changes in the area and shape of the cell nuclei. No significant effects on TEEI values were observed when 10 and 50 G 60 Hz magnetic fields were applied to confluent cell monolayers. There were no significant differences in migration and proliferation of the cell monolayer exposed to 60 Hz magnetic fields10 and 50 G , but a contact inhibition factor was observed. The expression of the CLDN-1 protein decreased by 90% compared with the control, while ZO-1 protein expression increased by 120%. No significant effects were observed in the area and shape of the cell nuclei. Experimentation in a controlled environment, under physiological conditions, ensures that the observed effects were strictly due to exposure to magnetic fields. Different exposure conditions are necessary to determine the impact on TEEI and cell migration–proliferation indicators. 相似文献
70.
E D Flores R A Lange R G Cigarroa L D Hillis 《Journal of the American College of Cardiology》1990,16(1):74-79
Cocaine increases myocardial oxygen demand and paradoxically decreases oxygen supply by reducing coronary blood flow. Such "inappropriate" vasoconstriction also occurs with exercise, which causes intense vasoconstriction of coronary artery segments narrowed by atherosclerosis. This study was done to assess the cocaine-induced change in vasomotor tone of diseased and nondiseased coronary artery segments. In 18 patients (15 men, 3 women, aged 35 to 67 years), coronary artery areas in diseased and nondiseased segments were quantitated before and 15 min after administration of intranasal saline solution (6 patients) or cocaine (2 mg/kg body weight) (12 patients). No variables changed after intake of the saline solution. In response to cocaine, the luminal areas of diseased and nondiseased segments decreased, but the magnitude of vasoconstriction was greater in the diseased segments (mean +/- SD 29 +/- 23% versus 13 +/- 8%, p less than 0.05). Thus, cocaine causes vasoconstriction of diseased and nondiseased coronary artery segments, but its effect is particularly marked in the former. 相似文献