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Comparison of Holsteins selected for high and average milk production. 1. Net income and production response to selection for milk.

The objective of the experiment was to quantify differences between two divergent lines of Holsteins for net income per day, per lactation, and per life-time using a linear profit function. Data consisted of 2768 lactation records from 1078 Holstein cows by 140 sires. Bulls with high PD milk were mated to daughters of sires with high PD for milk, and bulls with average PD for milk were mated to cows of average genetic merit, creating two divergent genetic lines of cattle. Data on production, health, and reproduction were collected. Analyses were based on lactation and lifetime. High line cows had greater net returns than average line cows by $.30/d (16.0%) per lactation and $.33 (19%) advantage/d of life. The high line cows were $103.79 more profitable (20.4%) per lactation and $375.60 (17.4%) more profitable during their lifetime than their average line herdmates. This income superiority was because high line cows averaged 940 kg more milk per lactation (16.4%) and 3435 kg more milk per lifetime (15.7%) than the average line cows. High line cows were superior by 500 kg for PTA for milk from January 1990. Selecting sires with high PD for milk effectively improved milk production and increased net income.

Animals↗

Visual selection mediated by location: feature-based selection of noncontiguous locations.

Experiments using two different methods and three types of stimuli tested whether stimuli at non-adjacent locations could be selected simultaneously. In one set of experiments, subjects attended to red digits presented in multiple frames with green digits. Accuracy was no better when red digits appeared successively than when pairs of red digits occurred simultaneously, implying allocation of attention to the two locations simultaneously. Different tasks involving oriented grating stimuli produced the same result. The final experiment demonstrated split attention with an array of spatial probes. When the probe at one of two target locations was correctly reported, the probe at the other target location was more often reported correctly than were any of the probes at distractor locations, including those between the targets. Together, these experiments provide strong converging evidence that when two targets are easily discriminated from distractors by a basic property, spatial attention can be split across both locations.

Choice Behavior↗

Cutting edge: characterization of allorestricted and peptide-selective alloreactive T cells using HLA-tetramer selection.

The vast majority of alloreactive T cells recognize foreign MHC molecules in a peptide-dependent manner. A subpopulation of these peptide-dependent alloreactive T cells is peptide-specific and contains T cells that are of interest for tumor immunotherapy. Allorestricted T cells (i.e., peptide-specific and alloreactive) specific for tumor-associated Ags can be raised in vitro. However, it is technically difficult to distinguish between peptide-specific and peptide-nonspecific alloreactive T cells by functional assays in vitro. Here we show for the first time that allorestricted T cells specifically bind HLA-peptide tetrameric complexes, as nominal Ag-specific T cells would do. In consequence, fluorescent HLA-peptide tetrameric complexes can be used for sorting and cloning of allorestricted CTLs specific for a peptide of interest. We also show by the mean of HLA-peptide tetramers the existence of peptide-selective alloreactive T cells that recognize a conformation on the foreign-MHC brought about by some but not all peptides bound.

Cell Line↗

Negative selection of T cells by Helicobacter pylori as a model for bacterial strain selection by immune evasion.

The majority of humans infected with Helicobacter pylori maintain a lifelong infection with strains bearing the cag pathogenicity island (PAI). H. pylori inhibits T cell responses and evades immunity so the mechanism by which infection impairs responsiveness was investigated. H. pylori caused apoptotic T cell death, whereas Campylobacter jejuni did not. The induction of apoptosis by H. pylori was blocked by an anti-Fas Ab (ZB4) or a caspase 8 inhibitor. In addition, a T cell line with the Fas rendered nonfunctional by a frame shift mutation was resistant to H. pylori-induced death. H. pylori strains bearing the cag PAI preferentially induced the expression of Fas ligand (FasL) on T cells and T cell death, whereas isogenic mutants lacking these genes did not. Inhibiting protein synthesis blocked FasL expression and apoptosis of T cells. Preventing the cleavage of FasL with a metalloproteinase inhibitor increased H. pylori-mediated killing. Thus, H. pylori induced apoptosis in Fas-bearing T cells through the induction of FasL expression. Moreover, this effect was linked to bacterial products encoded by the cag PAI, suggesting that persistent infection with this strain may be favored through the negative selection of T cells encountering specific H. pylori Ags.

Antigens, Bacterial↗

Selecting a Selective Serotonin Reuptake Inhibitor: Clinically Important Distinguishing Features.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat depression. Although these drugs presumably have the same mechanism of action, they vary in several clinically important ways, including how long they remain in the body and the extent to which they interfere with the metabolism of other medications. This article reviews the pharmacologic differences among SSRIs and how these differences may affect various aspects of treatment, such as dosing, administration, and discontinuation. Understanding the distinct properties of SSRIs may help primary care physicians to design the most appropriate therapeutic plan for individual patients.

Journal Article↗

Fetal nucleated erythrocyte recovery: fluorescence activated cell sorting-based positive selection using anti-gamma globin versus magnetic activated cell sorting using anti-CD45 depletion and anti-gamma globin positive selection.

BACKGROUND: Fluorescence activated cell sorting (FACS)-based anti-gamma (gamma) positive selection and magnetic activated cell sorting (MACS)-based anti-CD45 depletion followed by anti-gamma positive staining have been two of the most frequently used methods to isolate fetal cells from maternal blood. To date, there has been no direct comparison of fetal cell recovery by these two methods. This study was designed to address this issue. METHODS: Fluorescence in situ hybridization (FISH) was performed on nucleated anti-gamma positive cells using X and Y probes. Twenty-four maternal blood samples were obtained immediately after elective termination of pregnancy to ensure a detectable number of fetal cells. RESULTS: The yield and purity of fetal nucleated erythrocytes (FNRBCs) was statistically higher in FACS sorted samples (P < 0.01). The specificity of staining for FNRBCs was statistically higher in MACS sorted samples (P < 0.01). CONCLUSIONS: The data from this study demonstrate that both techniques have benefits and limitations. FACS has the advantage of having higher yield, higher purity, higher FISH efficiency and ease in microscope analysis, and MACS has the advantage of having higher specificity and less cell loss during FISH.

Antigens, CD↗

The duality of selection: excitatory and inhibitory processes in auditory selective attention.

Behavioral and event-related potential (ERP) measurements were made in an auditory selective-attention paradigm, both before and after a series of inhibition or discrimination training sessions. The presence of distractors caused poor perceptual sensitivity, weak P3 responses, conservative responding, and slow reaction times relative to baseline. Distraction prompted a frontal enhancement of ERP components occurring 100-250 ms after the onset of attended signals (N1, P2, and N2). Training ameliorated behavioral interference from distraction. Participants receiving inhibition training acquired improved inhibitory processing of distractors, an effect that peaked 200 ms after distractor onset. In a proposed model, distinct excitatory and inhibitory mechanisms work interactively to maintain sensitivity to environmental change in the face of disruption from the contextual integration of irrelevant events.

Acoustic Stimulation↗

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE Reserve Select for certain members of the selected reserve; Transitional Assistance Management Program; early eligibility for TRICARE for certain reserve component members. Interim final rule with comment period.

This interim final rule establishes requirements and procedures for implementation of TRICARE Reserve Select. It also revises requirements and procedures for the Transitional Assistance Management Program. In addition, it establishes requirements and procedures for implementation of the earlier TRICARE eligibility for certain reserve component members. The rule is being published as an interim final rule with comment period in order to comply with statutory effective dates.

Eligibility Determination↗

Effect of neurotransmitter-selective drugs in mice selected for differential sensitivity to the hypothermic actions of ethanol.

Mice selectively bred for resistance (HOT) and sensitivity (COLD) to the hypothermic effect of EtOH were tested for their hypothermic response to neurotransmitter-specific drugs and for the effect of such drugs on EtOH induced hypothermia (HT). The drugs administered were the opiate drugs morphine, levorphanol and U50488H, the dopamine agonists apomorphine, LY171535 and SKF38393, the dopamine antagonist chlorpromazine, the alpha adrenergic agonist St587, the cholinergic agonist nicotine and amphetamine, which increases the release of catecholamines. All of the drugs tested, with the exception of SKF38393 and amphetamine, induced a hypothermic response in HOT and COLD mice. SKF38393 had no effect on body temperature or HT produced by EtOH. Amphetamine caused HT at low doses and hyperthermia at high doses. COLD mice were more sensitive than HOT mice to the hypothermic effect of morphine and levorphanol, mu-opiate agonists, and U50488H, a relatively specific kappa agonist. All of the other drugs tested were approximately equally potent in HOT and COLD mice. These results suggest that the differential sensitivity of HOT and COLD mice to EtOH-induced HT may be partially mediated through genetic changes in opiate mechanisms.

Animals↗

Brown adipose tissue cell respiration in hypo- and hyperthyroidism after stimulation with selective and non selective beta-adrenergic agonists.

Brown adipocyte respiration was measured in isolated cells from hypothyroid, hyperthyroid and euthyroid Sprague-Dawley male rats. Hypothyroidism was induced by providing drinking water containing methimazole and hyperthyroidism was induced by addition of thyroid powder to the diet. Brown adipose tissue (BAT) cells were isolated by collagenase digestion and oxygen consumption (VO2) was measured by Clark type oxygen electrodes. BAT cell respiration was stimulated by selective and nonselective beta-adrenergic agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Basal BAT cells respiration did not differ according to thyroid status. Maximal VO2 responses of BAT adipocytes from hypothyroid rats were significantly lower than in euthyroidism after ISO and BRL. The reduced response was more marked for ISO than for BRL. The thermogenic sensitivity was significantly greater in euthyroid than is hypothyroid cells for ISO, but not for BRL. The euthyroid-hyperthyroid differences were not significantly different. These results suggest: basal respiration of BAT cells in hypo- and hyperthyroidism does not reflect the overall changes in whole body metabolism; the decreased thermogenic response in hypothyroidism might be due to decreased beta-adrenoceptor numbers and/or decreased intracellular thyroxine-triiodothyronine conversion; changes in sensitivity to ISO and BRL in vitro reflect the changes seen in VO2 in vivo.

Adipose Tissue, Brown↗

Studies on the comparative pharmacology and selective toxicity of tricaine methanesulfonate: metabolism as a basis of the selective toxicity in poikilotherms.

Tricaine methanesulfonate, administered at a dose of 150 mg/kg i.p., produced a flaccid paralysis and loss of the righting reflex in a number of poikilothermic species including the frog. Leopard frogs (Rana pipiens) given 150 mg/kg i.p. regained the righting reflex at 113 +/- 28 (S.D.) minutes after injection. A similar dose administered i.p. to mice produced no apparent pharmacological response. The biological half-life (T1/2) of tricaine in frogs (R. pipiens) was about 70 minutes at temperatures of 23 and 37.5 degrees C; at 7 degrees C the T1/2 was 309 minutes. In contrast, in the mouse the drug was metabolized so rapidly that 5 minutes after i.p. administration of 5 mg of tricaine methanesulfonate (250 mg/kg) none of the unchanged drug could be recovered from the animal. It was, however, recovered quantitatively as Bratton-Marshall reacting metabolites, including m-aminobenzoic acid. Incubations of tricaine with serum from bullfrogs, mice and humans indicated that the drug was metabolized to m-aminobenzoic acid with an apparent Km of 3 X 10(-3) M for the reaction. The Vmax for incubations of the drug with bullfrog and human serum was 40 nmol/min/ml of serum, whereas in mouse serum it was 93 nmol/min/ml of serum. In vitro studies with liver homogenates showed that mouse liver metabolized tricaine 39 times more rapidly than frog liver. We conclude, therefore, that the liver is the major site of tricaine hydrolysis in mammals and that the selective toxicity of tricaine for poikilotherms is a consequence of their slower rate of hepatic biotransformation of tricaine.

Aminobenzoates↗

Renal selective N-acetyl-L-gamma-glutamyl prodrugs. III. N-acetyl-L-gamma-glutamyl-4'-aminowarfarin is not targeted to the kidney but is selectively excreted into the bile.

The pharmacokinetics of N-acetyl-L-gamma-glutamyl-4'-aminowarfarin (AGAW) was studied in the rat. The aim of this prodrug was to cause a renal-specific inhibition of the vitamin K cycle as a result of renal-specific release of the active drug 4'-aminowarfarin (AW). In vitro, it was found that kidney and liver homogenates and cytosol were able to convert the prodrug. In vivo, plasma concentrations of AW rose only slowly after a dose of 10 mg/kg AGAW i.v. to give a maximum concentration of about 3 micrograms AW/ml at t = 14 to 24 h. The tissue distribution of AGAW and AW was measured after 10 mg/kg AGAW i.v. It was found that AGAW did not accumulate in the kidney (9.7 micrograms/g in the kidney; 83 micrograms/ml in plasma at t = 60 min). AW concentrations were very low (0.1 microgram/ml or mg at t = 60 min). These results suggest that AGAW is not transported via a carrier into the kidney. The uptake of AGAW in vitro by rat kidney slices was investigated. It was found that AGAW did not accumulate in the slices. Neither did AGAW influence the accumulation of N-acetyl-gamma-glutamyl sulfamethoxazole in kidney slices. A second explanation for the lack of selectivity of AGAW in vivo could be its high (approximately 90%) plasma protein binding. Instead of being targeted to the kidney, however, AGAW was found to be excreted via a carrier-mediated mechanism into the bile: 50% of the dose was recovered unchanged in the bile within 3 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The association of selected cancers with service in the US military in Vietnam. II. Soft-tissue and other sarcomas. The Selected Cancers Cooperative Study Group.

As part of a series of investigations into the health of Vietnam veterans, we conducted a population-based, case-control study of soft-tissue and other sarcomas between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible. Controls were selected by random-digit dialing. Analyses of 342 men with pathologically confirmed sarcoma and 1776 controls showed that Vietnam veterans had a relative risk of 1.0 for sarcoma in comparison with men who did not serve in Vietnam (95% confidence interval, 0.6 to 1.6). Restriction of the analysis to the 254 men with soft-tissue sarcoma yielded a relative risk of 0.9 (95% confidence interval, 0.5 to 1.6). Several attributes of military service in Vietnam (eg, branch, duration of service, military region, and other characteristics that may have been associated with the use of Agent Orange) were examined, and none was associated with an increased risk for the development of sarcoma. Furthermore, no morphologic type of sarcoma was overrepresented among Vietnam veterans. Results were unchanged if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. This study, which had 97% power to detect a relative risk of 2.0 for all sarcomas, provides no evidence that the risk for the development of soft-tissue or other sarcomas is increased among veterans 15 to 25 years following service in Vietnam.

Adult↗

Selective regulation of chemotactic lymphokine production. I. Selective potentiation of eosinophil chemotactic lymphokine production in alum hydroxy gel- and Bordetella pertussis vaccine-treated guinea pigs.

Delayed tissue eosinophilia in DNP-ovalbumin-induced allergic inflammatory skin lesions of guinea pigs was markedly enhanced by previous treatment with alum hydroxy gel (Alum) or Bordetella pertussis vaccine. This enhancement seemed due to increased production of a lymphocyte-derived eosinophil chemotactic factor (ECF) at the skin site. Treatment of animals with Alum potentiated antigen-induced in vitro ECF production by lymphoid cells from spleen and mesenteric lymph node of sensitized animals. The co-culture supernatants of lymphoid cells from Alum-treated animals also potentiated concanavalin A (Con A)-induced in vitro ECF production. The potentiating effect of Alum on ECF production seemed to be ascribed to the release of soluble factors from macrophages of the Alum-treated animals. The macrophage-derived soluble factor ECF-potentiating factor (ECF-PF) selectively potentiated ECF production but not macrophage chemotactic lymphokine production by Con A-stimulated lymphoid cells from normal animals. ECF-PF activity was associated with two separate m.w. fractions: one was 50,000 to 70,000 and the other was 10,000 to 20,000. The present study provides one of the explanations for enhanced ECF production by adjuvants, such as Alum and Bordetella pertussis vaccine.

Adjuvants, Immunologic↗

[Effect of selective and non-selective adrenoceptor blockade during physical work on energy metabolism and sympatho-adrenergic system (author's transl)].

The influence of an acute beta-adrenoceptor blockade on work capacity, oxygen intake, plasma catecholamines, and on energy metabolism was investigated in 9 healthy subjects during graduated ergometric exercise. The examinations were carried out after p.o. administration of 10 mg bunitrolol (BU), methypranol (ME) and placebo in random sequence. The exercise capacity shows a 15% decrease after both beta-blockers; heart rate shows a maximum 20% (BU) and 25% (ME) reduction, respectively. On account of the greater sympathetic intrinsic activity BU does not influence the resting heart rate, in contrast to ME (-8%; p greater than 0.05). BU leads to a decrease of the catecholamine levels (with low sympathetic tone), which is assumed to be caused by an effect on presynaptic receptors. At the same submaximum exercise levels plasma catecholamines are higher after BU and ME than after placebo; however, the maximum levels are not reached with placebo. In relation to the relative oxygen intake, which is inhibited by 4-6% by BU and ME (p greater than 0.05), the differences of the catecholamines decrease in performance caused by beta-blockade. BU does not show an influence on lactate, glucose, free fatty acids, and glycerin and thus represents a more selective blockade. ME inhibits lipolysis (measured by the glycerin level) by a maximum of approx. 50%. Lactate level increase is approx. 30% lower with ME. Glucose level decrease is approx. 20% higher with ME than with placebo.

Adrenergic beta-Antagonists↗

Critical evaluation of the diagnostic value of systolic time intervals in the diagnosis of functional thyroid diseases. Comparison of results in a highly selected and a non-selected group of patients in relation to the blood PBI and T4I levels.

The value of measuring systolic time intervals for the diagnosis of functional thyroid disorders was studied. We were able to confirm that the systolic time intervals, namely the preejection period (PEP) are significantly shortened in hyperthyroidism and protracted in hypothyroidism. We were able to prove the rectilinear correlation between the PEP interval and Ig PBI in both highly selected and unselected groups of untreated patients with thyroid disorders. We were able to show much lower diagnostic value of other systolic intervals (as Q-S2) and indices (Weissler's index) compared to PEP. We are able to enumerate some pathological cardiovascular states, where the PEP interval is considerably influenced. With due respect to above-mentioned problems, we are convinced that the PEP measurement is of real diagnostic value in the bed-side diagnosis of thyroid disorders, moreover we believe it might help to solve some theoretical problems.

Electrocardiography↗