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Use of selective and non-selective media for the isolation of Helicobacter pylori.

Antral biopsy specimens from patients having gastroduodenal disorders were cultured in parallel on sheep blood agar (SBA) and Skirrow's selective medium (SSM) for Helicobacter pylori. It was found that the overall isolation rate of the organism was much lower in SSM (54.5%) than on SBA (87.9%), a difference which is statistically significant (P less than 0.01). This may be due to the incorporation of polymyxin B in SSM. In absence of a suitable selective medium, blood agar may be used. Although consideration must be given to contamination, we found that contamination of SBA culture plates was not significant enough to hamper the isolation of the organism in the vast majority of the cases (98.5%).

Agar↗

Renal selective N-acetyl-gamma-glutamyl prodrugs. II. Carrier-mediated transport and intracellular conversion as determinants in the renal selectivity of N-acetyl-gamma-glutamyl sulfamethoxazole.

The mechanism of activation of the prodrug N-acetyl-L-gamma-glutamyl sulfamethoxazole (AGSM) and of gamma-glutamyl sulfamethoxazole (GSM) as a model for the mechanism of the renal selectivity of N-acetyl-gamma-glutamyl prodrugs was investigated. The hypothesis was tested that this selectivity is due largely to a carrier-mediated transport followed by an intracellular conversion of the prodrug to the active drug, in contrast to another mechanism. The transport of AGSM and GSM was studied with the use of kidney slices. AGSM accumulated in the slices. At 75 microM substrate concentration, the slice to medium ratio was 2.5 +/- 0.2. This accumulation was inhibited by the anion transport inhibitor probenecid (82% inhibition at 1.0 mM) and by the gamma-glutamyl transport inhibitor buthionine sulfoximine (60% at 1.0 mM). Acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid did not inhibit AGSM accumulation at 0.1 mM, a concentration sufficient to inhibit the enzyme gamma-glutamyl transpeptidase; at 1.0 mM, however, AGSM accumulation was inhibited by 44%. These results suggest that the accumulation of AGSM is caused by an active transport process. GSM did not accumulate in the slices, but was completely converted to sulfamethoxazole (SM) after a 90-min incubation. Accumulation of AGSM was also seen in vivo: at 20 min after AGSM administration (10 mg.kg-1) the plasma, kidney and liver concentrations were 73 +/- 6, 110 +/- 7 and 37 +/- 5 micrograms.g-1, respectively. This accumulation could be inhibited by buthionine sulfoximine but not by acivicin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kidney-selective prodrugs of 6-mercaptopurine: biochemical basis of the kidney selectivity of S-(6-purinyl)-L-cysteine and metabolism of new analogs in rats.

Recently, we have reported that S-(6-purinyl)-L-cysteine (PC) is a kidney-selective prodrug of 6-mercaptopurine. In the present study, the in vivo metabolism of PC and the biochemical basis of its renal selectivity were further investigated. In addition, several PC analogs were synthesized and evaluated as prodrugs of 6-mercaptopurine by determining the concentrations of 6-mercaptopurine and its metabolites, 6-methylmercaptopurine and 6-thiouric acid, in urine after rats were given the analogs. At 30 min after PC treatments, kidney metabolite concentrations were dependent on the PC dose at 40 to 130 mumol/kg and were not increased when a 400 mumol PC/kg dose was given. At the 400 mumol PC/kg dose, metabolite concentrations in the kidneys were higher at 30 min than at 1 or 3 hr, and were nearly 2.5- and 100-fold higher than those in liver and plasma, respectively. Rates of PC in vitro metabolism by liver and kidney cytosolic cysteine conjugate beta-lyases (beta-lyases) were similar, but metabolism by renal mitochondrial beta-lyase occurred at a 3-fold higher rate than the rate obtained with hepatic mitochondrial beta-lyase. When rats were given aminooxyacetic acid (500 mumol/kg) or probenecid (270 mumol/kg) before PC (130 mumol/kg), total kidney metabolite concentrations were reduced by 55 and 36%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminooxyacetic Acid↗

Modulation of the immune response to transplanted tumors in rats by selective depletion of neutrophils in vivo using a monoclonal antibody: abrogation of specific transplantation resistance to chemical carcinogen-induced syngeneic tumors by selective depletion of neutrophils in vivo.

The role of neutrophils in transplantation immunity to syngeneic rat tumors was examined using a monoclonal antibody (RP-3) that depletes rat neutrophils selectively in vivo. We used 2 chemical carcinogen-induced transplanted tumors of different antigenic specificity (KMT-17 and KDH-8 of WKA rat origin). When neutrophils were selectively depleted by i.p. injection of RP-3 at the time of in vivo priming with X-irradiated tumor cells, the growth of subsequently s.c. transplanted identical tumors was not inhibited, in contrast to the group of rats immunized without RP-3 treatment. Tumor growth was also not inhibited when the immune rats were treated with RP-3 at the time of identical viable tumor cell challenge. These results suggest that neutrophils play a role in both the priming and effector phases of specific transplantation resistance to syngeneic tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Selective nerve root block in patient selection for lumbar surgery: surgical results.

The cause of lumbar radicular symptoms often remains elusive after standard clinical and radiographic evaluation. Selective nerve root block is a useful test to indicate whether the pain is neural in origin and/or whether nerve root is pain producing in these patients with equivocal clinical and imaging studies. Over 8 years, the author performed selective nerve root blocks in 215 patients. Of this group, 78 patients underwent surgery. Following surgery, 71 patients were available for a minimum 12-month follow-up. The preoperative diagnoses included previously unoperated-upon lumbar disc herniation, previously unoperated-upon spinal canal stenosis, and prior lumbar surgery. The average follow-up was 34 months (range, 12-96 months). Overall, there were 38 good (53%), 16 fair (23%), and 17 poor (24%) surgical results. The results for those patients who had had prior surgery were disappointing (52% poor). These data reaffirm that surgical intervention should only be recommended for previously operated-upon patients with unequivocal findings.

Adolescent↗

Percutaneous selective thermorhizotomy in the treatment of "essential" trigeminal neuralgia. The importance of lesion selectivity.

Results following percutaneous thermorhizotomy for trigeminal neuralgia are described in 111 patients. Recurrences and side effects are more frequent whenever selectivity of the surgical lesion has been imperfect (exceeding the original pain area and causing marked hypoesthesia), and less frequent in the cases with strictly selective lesion.

Adult↗

Selective alpha-2 adrenoceptor blockade by SK&F 86466: in vitro characterization of receptor selectivity.

SK&F 86466 (6-chloro-N-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine) is a potent and selective antagonist at alpha-2 adrenoceptors. Prejunctional alpha-2 adrenoceptor antagonism can be demonstrated either by blockade of the alpha-2 adrenoceptor-mediated neuroinhibitory effect of clonidine or B-HT 920 in the guinea-pig atrium [receptor dissociation constant (KB) = 13-17 nM] or by potentiation of nerve-evoked release of [3H]norepinephrine from prelabeled guinea-pig atria, dog splenic artery or rabbit ear artery. Blockade of the postjunctional alpha-2 adrenoceptor was also seen, as demonstrated by a parallel shift to the right of the concentration-response curve for B-HT 920 as a constrictor agent in the dog saphenous vein. The KB for SK&F 86466 in this test system was 42 nM. The affinity of SK&F 86466 for the alpha-1 adrenoceptor is much lower, with a KB of 900 nM against norepinephrine-mediated constriction in the rabbit ear artery, or 1100 nM vs. SK&F 89748-induced constriction in the dog saphenous vein. The alpha-2/alpha-1 adrenoceptor selectivity ratio of SK&F 86466 is comparable to that obtained with agents such as yohimbine, making SK&F 86466 a useful tool for characterization of alpha-2 adrenoceptors and for investigation of their physiological role.

Adrenergic alpha-Antagonists↗

Conformational analysis of nisoxetine and fluoxetine, selective inhibitors of norepinephrine and serotonin reuptake: are conformational differences an explanation of neurotransmitter selectivity?

Low energy conformations and the pathways between them have been calculated for nisoxetine (N-methyl-3-phenyl-3-(o-methoxyphenoxy)-propylamine), (I), a selective inhibitor of neuronal reuptake of norepinephrine, and fluoxetine (N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine), (II), a selective inhibitor of neuronal reuptake of serotonin. Results are presented as a series of energy maps and ORTEP drawings. Conformational preferences of the protonated forms and preferred conformations in aqueous solution are also established. The CAMSEQ empirical potential method was used throughout. Both the nisoxetine and fluoxetine systems are shown to exhibit the known 'folded-extended' conformational preferences of the phenethylamines. It is suggested that the observed conformational variation between the two systems may play a role in the pharmacological differences between nisoxetine and fluoxetine.

Chemical Phenomena↗

Management of the selected term breech presentation: assessment of the risks of selected vaginal delivery versus cesarean section for all cases.

In this study, the concepts of decision theory have been applied to a clinical obstetric controversy--the management of the selected mature breech presentation. We have reviewed in detail the literature published since 1974 and estimated the probabilities of various outcomes after different treatment strategies. We conclude that a policy of selected vaginal delivery will result in four perinatal deaths for every 1000 patients delivered. A similar probability of neurologic handicap, at least until discharge from hospital, can also be attributed to this method of delivery. These unfavorable outcomes were reported less frequently in more recent reports covering the years since 1974. In these cases, the probability of fetal death due to a trial of vaginal delivery is approximately two in 1000. Cesarean section rates have risen, however, and 18-40% of trials of labor for breech presentation now result in "emergency" cesarean section. Decision analysis has demonstrated that a policy of elective cesarean section for all cases would not necessarily increase maternal mortality and morbidity. Thus the greater dangers of emergency compared with nonelective surgery may abolish the advantages of attempting a vaginal delivery. Depending on the relative dangers of elective and emergency cesarean section, planned delivery becomes the safer option when 16-30% of trials of vaginal breech delivery are unsuccessful. The strength and limitations of this probabilistic approach to the breech presentation are discussed in detail.

Adult↗

Pattern and motion vision in cats with selective loss of cortical directional selectivity.

Neurons in the visual cortex of cats reared in 8 Hz stroboscopic illumination show a profound loss of directional selectivity, but no detectable deficits in orientation selectivity, contrast sensitivity, and temporal frequency response, and only a slight reduction in spatial resolution. In the present study, spatial vision, temporal resolution, and a variety of motion detection and discrimination thresholds were examined behaviorally in such cats. These psychophysical measurements revealed nearly normal spatial and temporal vision, but severe abnormalities in visual discriminations based on differences in stimulus direction. Specifically, strobe-reared cats showed normal orientation discrimination and temporal frequency resolution, nearly normal contrast sensitivity at low spatial frequencies, and a slight reduction of sensitivity to high spatial frequencies. At high contrasts, the cats were able to discriminate opposite directions of motion over a wide range of visible speeds, and their performance was indistinguishable from that of normal cats. However, a comparison of contrast thresholds for detecting moving gratings and for discriminating their direction of motion revealed severe abnormalities in strobe-reared animals. At low spatial frequencies (0.28 cycles/deg), normal cats could discriminate the direction of grating motion at contrasts that were just barely visible, whereas the strobe-reared cats could detect the grating at contrasts similar to those required by normal cats, but required contrasts about 10 X the threshold to identify the direction of motion. Normal cats showed nearly identical contrast sensitivity for detecting and discriminating gratings of high spatial frequency at high temporal frequency (drift rates), but when the temporal frequency was low, their sensitivity for detection exceeded that for direction discrimination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selected fatty acids as possible intermediates for selective cytotoxic activity of anticancer agents involving oxygen radicals.

Both polyunsaturated fatty acids (PUFAs) and certain anticancer agents can generate peroxides leading to extensive lipid peroxidation. The link between peroxides, PUFAs and cell killing has been examined by testing the susceptibility of tumor cells to peroxides generated by PUFAs. Our results demonstrate that gammalinolenic, arachidonic and eicosapentaenoic acids are highly effective in killing human breast, lung, and prostate tumor cells while leaving normal cells viable. The availability of PUFAs and the role of lipoperoxidation are discussed with respect to the cytotoxic action of anticancer agents involving oxygen radicals. The results suggest that tumor cell susceptibility to lipid peroxides can be selectively modulated and manipulated by dietary PUFAs, especially those with 3 or more double bonds, and that the suggestion that non-selective toxicities of drugs are mediated by lipid peroxides must be viewed with caution.

Antineoplastic Agents↗

Verapamil-mediated sensitization of doxorubicin-selected pleiotropic resistance in human sarcoma cells: selectivity for drugs which produce DNA scission.

The effects of verapamil on the cytotoxicity and accumulation of multiple drugs were studied in a model of pleiotropic resistance generated by doxorubicin (DOX) selection of the human sarcoma cell line MES-SA. The in vitro sensitivity of the DOX-resistant variant (named Dx5), which is 50- to 100-fold resistant to DOX compared to MES-SA, was enhanced approximately 7-fold by verapamil (3 micrograms/ml). In addition, the cytotoxicity of several agents to which the Dx5 line displays cross-resistance, i.e., daunorubicin, dactinomycin, mitoxantrone, and etoposide, was also enhanced 2- to 14-fold by verapamil. These agents share the properties of DNA intercalation and/or interaction with topoisomerase II. In contrast, verapamil did not alter the sensitivity of Dx5 to several other agents to which cross-resistance had been demonstrated, i.e., vincristine, vinblastine, colchicine, mitomycin C, and melphalan; nor did verapamil enhance the cytotoxicity of DOX or other agents against the DOX-sensitive parent, MES-SA. The sensitizing effect of verapamil did not correlate well with its effects on intracellular drug accumulation. [14C]DPX accumulation was increased by 30-40% in Dx5 but not in MES-SA cells in the presence of verapamil. [3H]Vinblastine accumulation was increased by 24-72% in both MES-SA and Dx5 cells in the presence of verapamil, although cytotoxicity of the Vinca alkaloids was not affected. In this human sarcoma model of DOX-selected pleiotropic resistance, verapamil partially reversed the resistance to DOX, as well as four of the nine drugs for which cross-resistance had been demonstrated in Dx5. The potentiation by verapamil of the cytotoxicity of some but not all of these antitumor agents suggests that factors other than altered drug transport may be responsible. The pattern of sensitization, restricted to agents which produce DNA strand scission by interaction with topoisomerase II, suggests that verapamil may be acting to promote the formation or inhibit the repair of such DNA strand breaks.

Animals↗

Relative productivity of five selective plating agars for the recovery of Salmonella from selected food types.

During a 3-year period, the relative productivity of brilliant green (BG), bismuth sulfite (BS), Salmonella-Shigella (SS), Hektoen enteric (HE), and xylose lysine, desoxycholate (XLD) agars for recovering Salmonella from 9 food types was determined. Following pre-enrichment, selective enrichment of food samples in tetrathionate broth followed by streaking to BS agar was the single most productive selective enrichment broth-agar combination for recovery of Salmonella in 5 of these food types. A study of the performance of these 5 agars used individually and in various combinations, showed that none of the 5 agars used individually nor any of the possible paired combinations of these agars could be used to satisfactorily detect Salmonella in the 9 food types. The use of all 5 agars was not necessary because one combination of 4 agars (BG, BS, HE, and XLD) recoverd 100% of the Salmonella isolates, as compared with the number of Salmonella isolates recovered by the 5-agar combination, in each food category. This particular 4-agar combination, along with two 3-agar combinations (BG, BS, and XLD agars, and BS, HE, and XLD agars), were each able to recover more Salmonella isolates, than the combination of BG, BS, and SS agars, the combination currently recommended by the AOAC. Finally, the relative costs of using these agars, singly and in various combinations, were determined.

Agar↗

The effect of non-selective and selective beta-1-blockade on the plasma potassium response to hypoglycaemia.

The effect of non-selective beta-blockade with propranolol, beta 1-selective blockade with betaxolol and of saline on the plasma potassium response to insulin induced hypoglycaemia was examined in six healthy subjects. Although propranolol retarded the recovery from hypoglycaemia, the degree of hypokalaemia was significantly (p less than 0.01) less than with saline or betaxolol, which had similar effects. Adrenergic mechanisms may modulate potassium disposal through a beta 2 receptor.

Adrenergic beta-Antagonists↗

Biochemical approaches to enhancement of antitumor drug selectivity: selective protection of cells from 6-thioguanine and 6-mercaptopurine by adenosine.

The cytotoxicity of 6-thioguanine and 6-mercaptopurine to cultured lymphoblasts and fibroblasts was strongly antagonized by pretreatment of the cells with 100 microM adenosine. Administration of adenosine 2 hours after the antipurine agent did not cause antagonism. In two rat hepatoma cell lines, adenosine pretreatment did not protect cells from the antipurines. Treatment of lymphoblasts or fibroblasts with 100 microM adenosine gave increases up to 150% in cellular ATP and ADP and decreases greater than 80% in UTP and UDP. In the hepatoma lines, adenine nucleotides did not increase by greater than 45%, and uridine nucleotides did not decrease by greater than 40% following adenosine treatment. The selective protection of the normal cells from 6-thioguanine and 6-mercaptopurine was probably the consequence of phosphoribosylpyrophosphate (PRPP) depletion, since adenosine pretreatment decreased PRPP pools by greater than 90% in the normal cells but by only 30% in the malignant hepatoma cells. In the absence of PRPP the antipurines would not be metabolically activated. The selectivity of the adenosine and antipurine combinations was probably attributable to the low activity of adenosine kinase and high activities of adenosine deaminase and PRPP synthetase characteristic of malignant hepatomas.

Adenosine↗

Genetically selected winner and loser rats: what was selected?

Throughout the 6--12th generation, genetically selected winner and loser rats in the straight runway test, were studied, in relation to weight, open field behavior, behavioral responses to footshock and adrenocortical response following stimulation. The results showed that the Loser Runway Strain (LRS) when compared to the Winner Runway Strain (WRS), were (1) lighter in weight, (2) defecated less, ambulated more and showed higher frequency of rearing-up when submitted to an open field (3) defecated less and jumped more in reaction to footshock and (14) had a higher rise of corticosterone levels following handling or footshock. These differences between WRS--LRS are the same found between male-female rats. This conclusion does not favor the validity of the runway test as a social measure, and suggests that WSR--LRS were selected according to male-female characteristics instead of a winning or losing trait.

Animals↗

Extracellular catecholamine levels in rat hippocampus after a selective alpha-2 adrenoceptor antagonist or a selective dopamine uptake inhibitor: evidence for dopamine release from local dopaminergic nerve terminals.

The effect of 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-H-3-benzazepine (SKF 86466), a selective nonimidazoline alpha-2 adrenoceptor antagonist, on hippocampal release of norepinephrine and dopamine in conscious rats was investigated by in vivo microdialysis and high-pressure liquid chromatography. Additionally, extracellular concentrations of hippocampal dopamine (DA) and norepinephrine (NE), during infusion of selective monoamine uptake inhibitors, were determined in freely moving rats. The basal concentration of NE in the dialysate was 4.9 +/- 0.3 pg/20 microliters. Intravenous administration of 5 or 10 mg/kg of SKF 86466 was associated with a transient increase (30 min) of 2-fold (12 +/- 1 pg/20 microliters; P < .05) and 8-fold (39 +/- 3 pg/20 microliters; P < .05), respectively, in dialysate NE, whereas a 1-mg/kg dose had no effect. DA was not detected in basal dialysates, but after the administration of 5 or 10 mg/kg of SKF 86466, 3.9 +/- 0.4 and 6.4 +/- 0.6 pg/20 microliters, respectively, was present in the dialysates. The maximum increase in dialysate DA was reached 60 to 90 min after SKF 86466. The DA was not derived from plasma because plasma NE was elevated after the 5 mg/kg dose of SKF 86466 whereas no plasma DA was detected. In order to determine whether DA was present in noradrenergic nerve terminals, the dopamine beta-hydroxylase inhibitor SKF 102698 was administered (50 mg/kg i.p.). The inhibitor decreased dialysate NE but DA was still not detected in the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Chemically selected subclones of the CEM cell line demonstrate resistance to HIV-1 infection resulting from a selective loss of NF-kappa B DNA binding proteins.

To delineate cellular genes that are required for optimal HIV-1 infection, CEM cells were subjected to treatment with the chemical mutagen ethylmethanesulfonate (EMS) and subclones were selected based on their increased resistance to HIV-1 infection and reduced syncytium formation, despite relatively normal CD4 expression (20,000 to 25,000 receptors/cell). Two subclones with this phenotype demonstrated a diminished capacity of HIV-1 long terminal repeat-chloramphenicol acetyl transferase expression either after treatment with the protein kinase C activator PMA, or through Tat-mediated transactivation. In this study, we show that the cellular levels of the NF-kappa B DNA binding proteins (but not AP1 or SP1) are markedly reduced in these cell mutants both at the mRNA and protein levels, resulting in reduced nuclear localization of p50/p65 after PMA induction or treatment with the lymphokine TNF-alpha. Transient reconstitution with a plasmid expressing p50 resulted in partial recovery of PMA-inducible LTR-chloramphenicol acetyl transferase expression. These data suggest that, at least in the CEM T cell line, a selective reduction in the NF-kappa B DNA binding proteins is sufficient to curtail HIV-1 infection.

Base Sequence↗