Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We propose a protocol for determination of lactate threshold (LT) and test the validity of one aerobic training based on LT in rats. In group I, V(LTi) (velocity at LT before training) was determined in all rats (n=10), each rat training at its own V(LTi) and in group II, animals (n=7) ran at 15 m min(-1), the mean V(LTi) of group I. The training consisted of daily runs at V(LTi) for 50 min, 5 days/week, for 4 weeks. In group I, this program increased V(LT) (V(LTi) 14.90+/-1.49 m min(-1) and V(LTf), after training, 22.60+/-1.17 m min(-1)) and the velocity at exhaustion (19.50+/-1.63 m min(-1) and 27.60+/-1.17 m min(-1)). [Lactate] at LT (2.62+/-0.43 mmol L(-1) versus 2.11+/-0.15 mmol L(-1)) and relative values of LT (76+/-3% versus 82+/-2%) stayed unaltered. In group II the V(LTf) was 20+/-1.8 m.mim(-1), the [lactate] at the LT, 2.02+/-0.17 mmol.L(-1); the exhaustion speed, 23.57+/-2.11 m.mim(-1) and relative value of LT, 82.71+/-2.29%. There were no significant differences in these parameters between groups I and II. Thus, this protocol based on LT is effective and the mean V(LT) determined in a small number of healthy untrained rats can be used for aerobic training in a larger group of healthy animals of same gender and age.
Comp Biochem Physiol A Mol Integr Physiol 2005 Apr
PMID:Method for diagnosis and control of aerobic training in rats based on lactate threshold. 1593 99

The metabolic acidosis resulting from an intense exercise bout is large in crocodilians. Here we studied recovery from this pH perturbation in the American alligator. Metabolic rate, minute ventilation, arterial pH and gases, and strong ion concentration were measured for 10 h after exhaustion to elucidate the mechanisms and time course of recovery. Exhaustion resulted in a significant increase in lactate, metabolic rate, and ventilation, and a decrease in arterial PCO2), pH and bicarbonate. By 15 min after exhaustion, oxygen consumption returned to rest though carbon dioxide excretion remained elevated for 30 min. Arterial PO2), [Na+], and [K+], increased following exhaustion and recovered by 30 min post-exercise. Minute ventilation, tidal volume, [Cl-], and respiratory exchange ratio returned to resting values by 1 h. The air convection requirement for oxygen was elevated between 15 and 60 min of recovery. Breathing frequency and pH returned to resting values by 2 h of recovery. Lactate levels remained elevated until 6 h post-exercise. Arterial PCO2) and [HCO3-] were depressed until 8 h post-exercise. Compensation during recovery of acid-base balance was achieved by altering ventilation: following the initial metabolic acidosis and titration of bicarbonate, a relative hyperventilation prevented a further decrease in pH.
Comp Biochem Physiol A Mol Integr Physiol 2006 Mar
PMID:Recovery from an activity-induced metabolic acidosis in the American alligator, Alligator mississippiensis. 1644 82

Cytotoxic T lymphocytes (CTLs) are killer cells that are crucial in the control of viral pathogens and cancers. They can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of CTLs. Recently, Barber and colleagues demonstrated that B7-H1 (also called PD-L1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of T-cell exhaustion in a chronic-infection mouse model of lymphocytic choriomeningitis virus (LCMV). PD-1, the receptor of B7-H1, was greatly upregulated on CTLs in response to LCMV, and its expression was maintained during chronic infection. Blockade of the B7-H1-PD-1 pathway by a monoclonal antibody restored CTL function and reduced viral burden. These results suggest a new strategy for the treatment of chronic viral infection.
Trends Mol Med 2006 Jun
PMID:Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade. 1665 Aug 3

In response to nutrient limitation, Saccharomyces cerevisiae cells enter into a non-proliferating state termed quiescence. This transition is associated with profound changes in gene expression patterns. The adenine deaminase encoding gene AAH1 is among the most precociously and tightly downregulated gene upon entry into quiescence. We show that AAH1 downregulation is not specifically due to glucose exhaustion but is a more general response to nutrient limitation. We also found that Aah1p level is tightly correlated to RAS activity indicating thus an important role for the protein kinase A pathway in this regulation process. We have isolated three deletion mutants, srb10, srb11 and saf1 (ybr280c) affecting AAH1 expression during post-diauxic growth and in early stationary phase. We show that the Srb10p cyclin-dependent kinase and its cyclin, Srb11p, regulate AAH1 expression at the transcriptional level. By contrast, Saf1p, a previously uncharacterized F-box protein, acts at a post-transcriptional level by promoting degradation of Aah1p. This post-transcriptional regulation is abolished by mutations affecting the proteasome or constant subunits of the SCF (Skp1-Cullin-F-box) complex. We propose that Saf1p targets Aah1p for proteasome-dependent degradation upon entry into quiescence. This work provides the first direct evidence for active degradation of proteins in quiescent yeast cells.
Mol Microbiol 2006 May
PMID:Proteasome- and SCF-dependent degradation of yeast adenine deaminase upon transition from proliferation to quiescence requires a new F-box protein named Saf1p. 1667 11

Immunological studies of aging and of patients with chronic immune-mediated diseases document overlap of immune phenotypes. Here, the term "immune remodeling" refers to these phenotypes that are indicative of biological processes of deterioration and repair. This concept is explored through lessons from studies about the changes in the T-cell repertoire and the functional diversity of otherwise oligoclonal, senescent T cells. Immune remodeling suggests a gradual process that occurs throughout life. However, similar but more drastic remodeling occurs disproportionately among young patients with chronic disease. In this article, I propose that immune remodeling is a beneficial adaptation of aging to promote healthy survival beyond reproductive performance, but acute remodeling poses risk of premature exhaustion of the immune repertoire and, thus, is detrimental in young individuals.
Trends Mol Med 2007 Mar
PMID:Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. 1726 87

This paper compares the results of juvenile hormone (JH) titer determinations in two insect species, Melanoplus sanguinipes, a migratory grasshopper, and Acyrthosiphon pisum, the pea aphid, using a chiral-specific JH radioimmunoassay (RIA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), after extraction of JH with either hexane or isooctane-methanol. We compared results of JH titer determinations done on extracts of M. sanguinipes hemolymph taken from animals flown to exhaustion in tethered flight tests or unflown controls and from whole body extracts of A. pisum raised at two different temperatures. In each case the two different treatments experienced by the experimental animals were expected to result in widely differing JH titers. Methoprene and precocene II were used as internal standards. Samples were split and titers determined simultaneously with both the LC-MS/MS and RIA procedures. Unambiguous detection of JH III by LC-MS/MS was done by identification of its specific parent ion and its mass fingerprint (m/z 289, 267, 249, 235, 217, and 189). We conclude that isooctane-methanol-extracted JH samples can be accurately analyzed by LC-MS/MS, but not by RIA without further separation of JH from contaminating lipids. Hexane extracted JH samples from hemolymph can be analyzed accurately by both RIA and LC-MS/MS. However, the RIA results from whole body extracts of aphids reared at two different temperatures were initially obscured with excess lipids even when hexane was the extraction solvent. Thus samples were further purified by Waters Sep-Pak C18 column, but contaminating phospholipids continued to cause problems with the RIA assay. The detection limit of JH III standard for RIA was 13.75+/-2.39 pg whereas that for LC-M/MS was 8.25+/-1.44 pg in our experimental conditions.
Insect Biochem Mol Biol 2007 Aug
PMID:Comparison of radioimmunoassay and liquid chromatography tandem mass spectrometry for determination of juvenile hormone titers. 1762 78

Cholinergic Status, the total soluble circulation capacity for acetylcholine hydrolysis, was tested for putative involvement in individual variabilities of the recruitment of immune cells in response to endotoxin challenge. Young (average age 26) and elderly (average age 70) volunteers injected with either Escherichia coli endotoxin or saline on two different occasions were first designated Enhancers and Suppressors if they showed increase or decrease, respectively, in plasma acetylcholinesterase (AChE) activity 1.5 h after endotoxin administration compared to saline. Enhancers showed significant co-increases in plasma butyrylcholinesterase (BChE) and paraoxonase (PON1) activities, accompanied by rapid recovery of lymphocyte counts. Young Enhancers alone showed pronounced post-exposure increases in the pro-inflammatory cytokine interleukin-6 (IL-6), and upregulation of the normally rare, stress-induced AChE-R variant, suggesting age-associated exhaustion of the cholinergic effects on recruiting innate immune reactions to endotoxin challenge. Importantly, IL-6 injected to young volunteers or administered in vitro to primary mononuclear blood cells caused upregulation of AChE, but not BChE or PON1, excluding it from being the sole cause for this extended response. Interestingly, Suppressors but not Enhancers showed improved post-exposure working memory performance, indicating that limited cholinergic reactions may be beneficial for cognition. Our findings establish Cholinergic Status modulations as early facilitators and predictors of individual variabilities in the peripheral response to infection.
J Mol Med (Berl) 2007 Nov
PMID:Cholinergic status modulations in human volunteers under acute inflammation. 1765 67

Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion of the spermatogonial stem cell population. This is likely due to the deregulated expression of genes controlling the switch between spermatogonial self-renewal and differentiation. Here we show that Plzf directly represses the transcription of kit, a hallmark of spermatogonial differentiation. Plzf represses both endogenous kit expression and expression of a reporter gene under the control of the kit promoter region. A discrete sequence of the kit promoter, required for Plzf-mediated kit transcriptional repression, is bound by Plzf both in vivo and in vitro. A 3-bp mutation in this Plzf binding site abolishes the responsiveness of the kit promoter to Plzf repression. A significant increase in kit expression is also found in the undifferentiated spermatogonia isolated from Plzf(-/-) mice. Thus, we suggest that one mechanism by which Plzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression.
Mol Cell Biol 2007 Oct
PMID:Repression of kit expression by Plzf in germ cells. 1766 82

Escherichia coli responds to nutrient exhaustion by entering a state commonly referred to as the stationary phase. Cells entering the stationary phase redirect metabolic circuits to scavenge any available nutrients and become resistant to different stresses. However, many DNA repair pathways are downregulated in stationary-phase cells, which results in increased mutation rates. DNA repair activity generally depends on consumption of energy and often requires de novo proteins synthesis. Consequently, unless stringently regulated during stationary phase, DNA repair activities may lead to an irreversible depletion of energy sources and, therefore to cell death. Most stationary phase morphological and physiological modifications are regulated by an alternative RNA polymerase sigma factor RpoS. However, nutrient availability, and the frequency and nature of stresses, are different in distinct environmental niches, which impose conflicting choices that result in selection of the loss or of the modification of RpoS function. Consequently, DNA repair activity, which is partially controlled by RpoS, is differently modulated in different environments. This results in the variable mutation rates among different E. coli ecotypes. Hence, the polymorphism of mutation rates in natural E. coli populations can be viewed as a byproduct of the selection for improved fitness.
Crit Rev Biochem Mol Biol
PMID:Causes and consequences of DNA repair activity modulation during stationary phase in Escherichia coli. 1768 68

CD20 is a cell-surface marker expressed on mature B cells and most malignant B cells, but not stem or plasma cells. It is an ideal target for monoclonal antibodies (mAb), such as rituximab and ofatumumab, as it is expressed at high levels on most B-cell malignancies, but does not become internalized or shed from the plasma membrane following mAb treatment. This allows mAb to persist on the cell surface for extended periods and deliver sustained immunological attack from complement and FcR-expressing innate effectors, particularly macrophages. CD20 can also generate transmembrane signals when engaged by certain mAb which, although unproven, might provide an important element of the therapeutic success of anti-CD20 mAb. These favourable characteristics have led to anti-CD20 mAb being developed and exploited for use in immunotherapy, where they have proven remarkably efficacious in both the treatment of malignant disease and autoimmune disorders by deleting malignant or normal B cells, respectively. In this review, we discuss how these mAb have driven research in the immunotherapy field over the last decade, detail their likely modes of action and their limitations in terms of effector exhaustion, and explore ways in which they might be enhanced and further exploited in the future.
Mol Immunol 2007 Sep
PMID:Mechanisms of killing by anti-CD20 monoclonal antibodies. 1776


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>