PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Functional potential”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2002

Calcium modulation of adherens and tight junction function: a potential mechanism for blood-brain barrier disruption after stroke.

BACKGROUND: This review deals with the role of calcium in endothelial cell junctions of the blood-brain barrier (BBB). Calcium is critical for adherens junction function, but it appears that calcium is also important in regulating tight junction function necessary for the barrier characteristics of cerebral microvessels. SUMMARY OF REVIEW: The BBB is critical for brain homeostasis and is located at the cerebral microvessel endothelial cells. These endothelial cells maintain their barrier characteristics via cell-cell contacts made up of adherens and tight junctions. Adherens junctions are calcium dependent; recent evidence suggests that calcium also affects tight junctions. After stroke, there is a disruption of the BBB. Interfering with calcium flux under hypoxic conditions can prevent BBB breakdown. Calcium may alter BBB junction integrity by a number of different signal transduction cascades, as well as via direct interaction of calcium ions with junction proteins. It remains to be determined whether clinical use of calcium channel antagonists is a viable means to reduce BBB disruption after stroke. CONCLUSIONS: With the widespread use of calcium channel blockers as clinical treatments for hypertension, which is a risk factor for stroke, the exact role of calcium in modulating BBB integrity needs to be elucidated.

Adherens Junctions↗
PubMed2003

LY503430, a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor potentiator with functional, neuroprotective and neurotrophic effects in rodent models of Parkinson's disease.

Glutamate is the major excitatory transmitter in the brain. Recent developments in the molecular biology and pharmacology of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors have led to the discovery of selective, potent, and systemically active AMPA receptor potentiators. These molecules enhance synaptic transmission and play important roles in plasticity and cognitive processes. In the present study, we first characterized a novel AMPA receptor potentiator, (R)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430), on recombinant human GLUA1-4 and native preparations in vitro and then evaluated the potential neuroprotective effects of the molecule in rodent models of Parkinson's disease. Results indicated that submicromolar concentrations of LY503430 selectively enhanced glutamate-induced calcium influx into human embryonic kidney 293 cells transfected with human GLUA1, GLUA2, GLUA3, or GLUA4 AMPA receptors. The molecule also potentiated AMPA-mediated responses in native cortical, hippocampal, and substantia nigra neurons. We also report here that LY503430 provided dose-dependent functional and histological protection in animal models of Parkinson's disease. The neurotoxicity after unilateral infusion of 6-hydroxydopamine into either the substantia nigra or the striatum of rats and that after systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice were reduced. Interestingly, LY503430 also had neurotrophic actions on functional and histological outcomes when treatment was delayed until well after (6 or 14 days) the lesion was established. LY503430 also produced some increase in brain-derived neurotrophic factor in the substantia nigra and a dose-dependent increases in growth associated protein-43 (GAP-43) expression in the striatum. Therefore, we propose that AMPA receptor potentiators offer the potential of a new disease modifying therapy for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design.

The peripheral anionic site of acetylcholinesterase lies at the entrance to the active site gorge. It is composed of five residues (Tyr 70, Asp 72, Tyr 121, Trp 279 and Tyr 334; Torpedo numbering); associated with it are a number of surface loops, conferring a high degree of conformational flexibility on the area. The site is involved in the allosteric modulation of catalysis at the active centre and is the target of various anti-cholinesterases. It is also implicated in a number of non-classical functions, in particular, amyloid deposition, cell adhesion and neurite outgrowth. A number of peptide and protein ligands for the site have been identified. In this review, the structure and multiple functions of the peripheral anionic site are discussed, together with its potential as a target in rational drug design for the development of novel and improved inhibitors and of therapeutics for the treatment of neural cancers, nerve regeneration and neurodegenerative disorders such as Alzheimer's disease.

Acetylcholinesterase↗
PubMed1991

High-dose aprotinin (trasylol) in reducing bleeding and protecting lung function in potential bleeders undergoing cardiopulmonary bypass.

Intraoperative high-dose aprotinin during cardiopulmonary bypass was used to investigate if high-risk bleeders could be changed to bleed normally or less as well as see if aprotinin could preserve lung function. Eleven matched controls were compared with eleven aprotinin patients taking warfarin or aspirin preoperatively. The mean (+/- SEM) 12-h and 24-h postoperative amount of bleeding, volume of blood product transfusion and hemoglobin reduction in the aprotinin group were 328 +/- 45 ml, 418 +/- 63 ml, 341 +/- 99 ml and 1.8 +/- 0.5 g% respectively, which were significantly lower than the respective values of 716 +/- 86 ml (P less than 0.01), 1,029 +/- 115 ml (P less than 0.01), 985 +/- 294 ml (P less than 0.05) and 4.1 +/- 0.4 g% (P less than 0.02) in the controls. There was a 65% blood-saving effect by aprotinin in this study. The hypercapnea rate was 45% in the treated patients, and 82% (P less than 0.05) in the controls reflecting better preservation of pulmonary diffusion function which is clinically important following major surgery.

Aged↗
PubMed2004

Memory T cells in transplantation: generation, function, and potential role in rejection.

The adaptive immune system is endowed with long-lived memory to recall previous antigen encounters and respond more effectively to them. Memory immune responses are mediated by antigen-specific memory T lymphocytes that exhibit enhanced function compared with naïve T cells that have never encountered antigen. While the generation of memory T cells specific for pathogens is beneficial in providing protective immunity, memory T cells specific for alloantigens can be deleterious to the recipient of a transplanted organ. In graft rejection, memory T cells mediate accelerated, "second-set" rejection and their presence has been associated with increased propensity for early rejection. Recent findings have demonstrated that alloreactive memory T cells can be generated via exposure to alloantigens, as well as stimuli that are cross-reactive with alloantigens, and are therefore likely present in "naïve" individuals. This review focuses on the characteristics of memory T cells which make them of special interest to the transplant community, including differential activation requirements, broad homing properties, and resistance to tolerance induction. The multiple ways in which memory T cells can contribute to early and late graft rejection are discussed, as well as potential targets for combating alloreactive memory to be considered in the future design of tolerance induction strategies.

Animals↗
PubMed1978

Prostaglandins: renin release and renal function.

Renal prostaglandins have several potential functions in renal physiology. Perhaps their best documented role is the maintenance of renal blood flow during renal ischemia, although they are apparently not essential to blood flow autoregulation in the absence of ischemia. Alterations in sodium excretion parallel the hemodynamic changes induced by prostaglandin infusions and prostaglandin inhibition with indomethacin. A direct action on sodium balance is unproven. Numerous studies, in vivo and in vitro, have convincingly demonstrated that prostaglandins or their precursors stimulate renin release and prostaglandin inhibition blunts renin release independent of hemodynamic and electrolyte balance. These functions of prostaglandins have implicated them in the manifestations of Bartter's syndrome, the nephropathy of liver cirrhosis, renovascular hypertension, and other nephropathies.

Animals↗
PubMed2001

IL-7 administration alters the CD4:CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation.

IL-7 is vital for the development of the immune system and profoundly enhances the function of mature T cells. Chronic administration of IL-7 to mice markedly increases T cell numbers, especially CD8(+) T cells, and enhances T cell functional potential. However, the mechanism by which these effects occur remains unclear. This report demonstrates that only 2 days of IL-7 treatment is needed for maximal enhancement of T cell function, as measured by proliferation, with a 6- to 12-fold increase in the proportion of CD4(+) and CD8(+) T cells in cell cycle by 18 h of ex vivo stimulation. Moreover, a 2-day administration of IL-7 in vivo increases basal proliferation by 4- and 14-fold in CD4(+) and CD8(+) T cells, respectively. These effects occur in the absence of cytokine production, increases in most activation markers, and changes in memory markers. This enhanced basal proliferation is the basis for the increase in T cell numbers in that IL-7 induces an additional 60% and 85% of resting CD4(+) and CD8(+) T cells, respectively, to enter cell cycle in mice given IL-7 for 7 days. These results demonstrate that in vivo administration of IL-7 increases T cell numbers and functional potential via a homeostatic, nonactivating process. These findings may suggest a unique clinical niche for IL-7 in that IL-7 therapy may increase T cell numbers and enhance responses to specific antigenic targets while avoiding a general, nonspecific activation of the T cell population.

Animals↗
PubMed1999

Origins, functions, and potential of adult neural stem cells.

In recent years, the existence of neural stem cells (NSCs) in the adult mammalian brain has been confirmed. The generation of new neurons from these cells is regulated by growth factors, hormones, and environmental cues; however, the function of newly generated neurons in the adult brain remains elusive. Two recent articles emphasize the impact of motor activity and learning on in situ hippocampal neurogenesis,((1,2)) suggesting a close link to hippocampal function. Adult NSCs can be isolated and expanded in vitro. It was presumed that the origins of the NSCs were within subependyma of the lateral ventricle; however, new evidence suggests that the "real" stem cells may reside in the ependymal lining.((3)) In a related study, these same cells were transplanted into irradiated mice and were able to integrate into the bone marrow and produce various blood cell types,((4)) challenging the limits of neural cell fate determination.

Animals↗
PubMed2005

Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population.

p73, a structural and functional homologue of p53, shares some p53-like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell-cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case-control study of 425 lung cancer patients and 588 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26-0.80 and OR: 0.70, 95% CI: 0.53-0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele.

Aged↗
PubMed2026

Genome-wide cyclin gene evolution in Arabidopsis and Brassica reveals polyploidization-driven duplication and flowering-time associations.

Cyclin genes are plant cell cycle regulators that play essential roles in growth, development, and reproduction. However, the evolutionary dynamics and genomic organization of cyclin genes across the Brassicaceae family remain poorly understood, particularly in the context of allotetraploid genome evolution. Here, we investigated the diversity, expansion mechanisms, and potential functional diversification of cyclin genes across ten Brassicaceae genomes, including four Arabidopsis and six Brassica species. A total of 1087 cyclin genes representing 23 cyclin types were identified. Comparative genomic analyses revealed that cyclin gene expansion was strongly influenced by polyploidization in Brassica species, with 1845 duplication events involving 1063 genes. Whole-genome duplication was the predominant mechanism driving expansion, while both inter- and intra-genomic duplications contributed to gene retention in tetraploid Brassica species, with the highest duplication frequency observed in Brassica juncea. Across genomes, 120 physical gene clusters were identified, including homogeneous and heterogeneous types. Ortholog analysis between progenitor and allotetraploid species identified 852 orthologous pairs involving 366 genes, indicating extensive conservation following allotetraploid formation. Phylogenetic analysis resolved cyclins into three major clades, while expression-based clustering in Brassica napus grouped genes into four major clusters, suggesting functional diversification. Integration of pan-genomic and flowering-time QTL analyses further identified two cyclin genes, Bna21cycA2 and Bna113cycD4, which contain amino acid polymorphisms and represent putative candidate variations potentially associated with flowering-time variation across multiple genomes. These findings provide new insights into the evolutionary expansion, retention, and potential functional divergence of cyclin genes in Brassicaceae and highlight candidate loci for future functional studies and crop improvement.

Evolution, Molecular↗
PubMed1990

The C gamma 1-encoded disulphide-linked and the C gamma 2-encoded nondisulphide-linked forms of the gamma/delta heterodimer use different gamma and delta variable regions.

We identified two types of gamma/delta T-cell clones: (1) BB3+ clones, which express the disulphide-linked form of the gamma/delta heterodimer (type 1 receptor) and carry rearrangements of the C gamma 1 gene; and (2) delta TCS1+ clones, which express the nondisulphide-linked form of the gamma/delta heterodimer (type 2 receptor) and carry rearrangements of the C gamma 2 gene. To determine the joining (J) and variable (V) region usage of the two receptor types, T gamma and T delta gene rearrangements and expression were analyzed in each gamma/delta T-cell clone. The results showed that the J and V regions used by the two receptor types are distinct: clones that express the type 1 receptor carry potentially functional rearrangements in J gamma P-V gamma 9 for gamma and in J delta 1-V delta 2 for delta; and clones that express the type 2 receptor had potentially functional rearrangements in J gamma 2-V gamma 2/V gamma 4 for gamma and in J delta 1-V delta 1 for delta. Therefore, two clearly different gamma/delta receptors (V gamma 9-J gamma P-C gamma 1/V delta 2-J delta 1-C delta and V gamma 2/V gamma 4-J gamma 2-C gamma 2/V delta 1-J delta 1-C delta) predominate in peripheral blood.

Adult↗