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PubMed2002

Selective strand annealing and selective strand exchange promoted by the N-terminal domain of hepatitis delta antigen.

We have previously shown that the N-terminal domain of hepatitis delta virus (NdAg) has an RNA chaperone activity in vitro (Huang, Z. S., and Wu, H. N. (1998) J. Biol. Chem. 273, 26455-26461). Here we investigate further the basis of the stimulatory effect of NdAg on RNA structural rearrangement: mainly the formation and breakage of base pairs. Duplex dissociation, strand annealing, and exchange of complementary RNA oligonucleotides; the hybridization of yeast U4 and U6 small nuclear RNAs and of hammerhead ribozymes and cognate substrates; and the cis-cleavage reaction of hepatitis delta ribozymes were used to determine directly the role of NdAg in RNA-mediated processes. The results showed that NdAg could accelerate the annealing of complementary sequences in a selective fashion and promote strand exchange for the formation of a more extended duplex. These activities would prohibit NdAg from modifying the structure of a stable RNA, but allow NdAg to facilitate a trans-acting hammerhead ribozyme to find a more extensively matched target in cognate substrate. These and other results suggest that hepatitis delta antigen may have a biological role as an RNA chaperone, modulating the folding of viral RNA for replication and transcription.

Base Sequence↗
PubMed1981

Adsorption, desorption, potential and selective distribution of heavy metals in selected soils of Japan.

Adsorption, desorption, potential and selective distribution of Cu, Zn, Cd, Pb and Ni were investigated in three typical soils of Japan under flooded condition. The results indicate that the sorption of all heavy metals was linear upto the maximum concentration (500 micrograms/g soil) employed in the present studies in all the soils. The magnitude of sorption in general was in the order of Pb greater than Cu greater than Zn greater Cd greater than Ni. The adsorption coefficients showed wide variation among different soils as well as metal ions. The hysteresis of sorption and desorption by KN03 was well pronounced for both the metal ions and the soils. The desorption rate was greater than the fixation rate indicating the predominance of the chemosorption over physical processes. The major portion of sorbed metals were retained in the unextractable form, which over all accounted for more than 50% of the sorbed metals.

Adsorption↗
PubMedDate not supplied

When familiar social partners are selected in open-ended situations: further tests of the socioemotional selectivity theory.

Socioemotional selectivity theory (SST; Carstensen, 1995, Current Directions in Psychological Science, 4, 151-156) predicts that novel social partners are preferred in open-ended situations, whereas familiar social partners are preferred in future-limited situations. The authors attempted to generalize past research to new familiar and novel partner options. Studies 1 (N=144; undergraduates, community-dwelling adults ages 65 to 95) and 2 (N=336 community-dwelling participants ages 11 to 89) indicated that young and older participants in a future-limited situation preferred familiar partners. However, with different social partner options than have been used in previous research, young participants in an open-ended situation also preferred a familiar partner, contrary to the predictions of SST.

Adaptation, Psychological↗
PubMed1980

Ionic selectivity, saturation, and block in a K+-selective channel from sarcoplasmic reticulum.

The open-channel conductance properties of a voltage-gated channel from sarcoplasmic reticulum were studied in planar phospholipid membranes. The channel is ideally selective for K+ over Cl- and for K+ over Ca++. In symmetrical 1 M solutions, the single-channel conductance (in pmho) falls in the order: K+ (214) > NH4+ (157) > Rb+ (125) > Na+ (72) > La+ (8.1) > Cs+ (< 3). In neutral bilayers, the channel conductance saturates with ion activity according to a rectangular hyperbolic relation, with half-saturation activities of 54 mM for K+ and 34 mM for Na+. Under symmetrical salt conditions, the K+:Na+ channel conductance ratio increases with salt activity, but the permeability ratio, measured by single-channel bi-ionic potentials, is constant between 20 mM and 2.5 M salt; the permeability ratio is equal to the conductance ratio in the limit of low-salt concentration. The channel conductance varies < 5% in the voltage range -100 to +70 mV. The maximum conductance varies K+ and Na+ is only weakly temperature dependent (delta H++ = 4.6 and 5.3 kcal/mol, respectively), but that of Li+ varies strongly with temperature (delta H++ = 13 kcal/mol). The channel's K+ conductance is blocked asymmetrically by Cs+, and this block is competitive with K+. The results are consistent with an Eyring-type barriers as it permeates the channel. The data conform to Lüger's (1973. Biochem. Biophys. Acta. 311:423-441) predictions for a "pure" single-ion channel.

Animals↗
PubMed2004

The NMDA NR2B subunit-selective receptor antagonist, CP-101,606, enhances the functional recovery the NMDA NR2B subunit-selective receptor and reduces brain damage after cortical compression-induced brain ischemia.

Using a novel in vivo model for cerebral ischemia produced by short-lasting compression of a well-defined brain area of sensorimotor cortex we studied neuroprotective effects of the NMDA NR2B subunit selective antagonist, CP-101,606, in Sprague-Dawley rats. Cortical compression for 30 min produced a consistent and highly reproducible functional impairment, that is paresis of contralateral hind and fore limbs. The neurological deficit was accompanied by marked brain damage in cerebral cortex, hippocampus and thalamus as identified by Fluoro-Jade, a marker of general neuronal cell death. Using a daily performed beam walking test it was shown that untreated animals recovered from their functional impairment within 5-7 days following surgery. Intravenous administration of increasing doses (1, 5, 10, 20 mg/kg) of the NMDA NR2B subunit receptor specific antagonist, CP-101,606, dose-dependently improved the rate of functional recovery and protected against the ischemic brain damage in cerebral cortex, hippocampus, and thalamus as identified 2 days after the ischemic insult. Based upon these results, we conclude that NMDA NR2B receptor subunits represent potential targets to reduce not only the functional deficits, but also neuronal death in cortex and several midbrain regions produced by moderate, transient, cerebral ischemia.

Animals↗
PubMed1994

Preferential TCR V usage in rat repertoire selection: V alpha 8 imparts both positive thymic selection by and alloreactivity to RT1f.

Using a panel of newly developed mAb to two rat TCR V alpha and four TCR V beta segments, TCR V usage in CD4 and CD8 T cells of eight RT1 congenic strains sharing the LEW background was analyzed by flow cytometry. While no striking effects on V beta 8.2 and 8.5 usage were observed, a 3- to 4-fold over-representation of V beta 10 in the CD4 as compared with the CD8 subset in all strains suggested a preference of V beta 10 for MHC class II products. The degree of 'overselection' was mapped to the RT1.B/D region. In addition, an allele-specific overselection of V alpha 4+ CD4 T cells was mapped to RT1.B/Du and of V beta 16+ CD8 T cells to RT1.Au. Finally, a dramatic overselection of V alpha 8+ CD8 T cells by RT1f (14% in RT1f versus 1-2% in other haplotypes) provides the most striking case yet for an intrinsic affinity of a TCR V segment for an MHC product. V alpha 8+ CD8 T cells are not only overselected by RT1f in the thymus, but also during the alloreactive response of peripheral CD8 T cells to RT1f. The implications of these findings for the contribution of TCR V segments to TCR-MHC interactions in repertoire selection and alloreactivity are discussed.

Animals↗
PubMed2004

Combination of S1 nuclease and PNA for site-selective hydrolysis of double-stranded DNA. Comparison with the site-selective hydrolysis using Ce(IV)/EDTA.

The potential of the combination of SI nuclease and pseudo-complementary PNA (pcPNA) for site-selective scission of double-stranded DNA has been investigated. Through strand invasion of two pcPNAs, single-stranded portions were formed in both strands of substrate DNA. In the initial stage of the enzymatic digestion, two scission fragments were obtained due to the hydrolysis at these two gap-like sites. On prolonged reactions, however, these products (as well as the substrate DNA) were further digested to smaller fragments. Under the conditions employed here, only Ce(IV)/EDTA is available for the preparation of desired fragments from double-stranded DNA.

Cerium↗
PubMed2003

Free diet selection by broilers as influenced by dietary macronutrient ratio and corticosterone supplementation. 1. Diet selection, organ weights, and plasma metabolites.

Male broiler chickens (aged 21 d) were allowed to chose freely for 14 d between three diets in which only one specific macronutrient (protein, lipid, or carbohydrate) was isocalorically substituted for one other macronutrient, but otherwise (nearly) isocaloric and composed of the same ingredients. The three diets were low protein (LowCP; 15.81% CP; 6.56% lipid; 50.78% carbohydrate), low lipid (LowL; 19.63% CP; 3.01% lipid; 51.12% carbohydrate), and low carbohydrate (LowCHO; 19.50% CP; 7.72% lipid; 44.00% carbohydrate). The chickens either received 0, 30, or 45 mg of corticosterone (CORT) per kg diet. As a percentage of their total intake, unsupplemented chickens consumed 24.0, 71.4, and 4.6% of the LowCP, LowL, and LowCHO diets, respectively, giving a total CP, L, and CHO intake of 282, 61, and 765 g, respectively. The addition of CORT significantly changed the diet selection, as compared to the unsupplemented chickens, CORT chickens consumed a greater percentage from the LowCP (35%), less from the LowL (55%), and again more from the Low-CHO (10%) diet. On the other hand, total feed consumption, macronutrient, and ME intake were not altered significantly by CORT supplementation, probably because of the close similarity of the diets. Corticosterone-supplemented chickens manifested hyperglycemia, hyperlipidemia, and uric acidemia suggesting insulin resistance, increased lipogenesis and protein catabolism, respectively. The elevated plasma creatine kinase (CK) activities of CORT chickens are also suggestive for decreased muscle cell membrane stability. Furthermore, CORT chickens were characterized by increased proportional weights of liver, abdominal fat pad, proventriculus, and gizzard, whereas an involution of spleen and bursa was observed. In conclusion, the present results suggest that high circulating levels of CORT as in the case of stress results in metabolic alterations, which in turn, affects diet preference as a compensatory mechanism to adapt energy and nutrient metabolism.

Adipose Tissue↗
PubMed2006

Re-engineering healthcare pipelnes: why trajectory selection is as important as process selection in enabling effective transfer of best practice.

PURPOSE: To demonstrate that effective re-engineering of healthcare pipelines requires selecting both the "best" process (how we shall do it in the future) and the best trajectory for change (how we get from here to there). DESIGN/METHODOLOGY/APPROACH: Exploitation of Braess' Paradox to identify strategic factors necessary to enable change in the re-engineering of NHS healthcare pipelines. FINDINGS: Route to maximising the chance of achieving effective change is displayed via a Johari Window. Each cell is then related to no change (despite significant investment); failure; or successful implementation. RESEARCH LIMITATIONS/IMPLICATIONS: The demonstrator pipeline is an NHS cataract repair supply chain. However, via the "Power of Analogy" concept the NHS scenario is readily related to a substantial number of industrial case studies. PRACTICAL IMPLICATIONS: The need to understand both process and trajectory is the key to effective re-engineering of pipelines. All "actors" in re-engineering programmes should acquire this knowledge and benefit from the new way of doing things. ORIGINALITY/VALUE: Formalises the strategic route to enabling healthcare delivery "best practice".

Health Care Reform↗
PubMed1979

Non-selective and selective beta-1-adrenoceptor blocking agents in the treatment of hyperthyroidism.

Treatment for one month with propranolol or atenolol, a selective beta-1-adrenoceptor blocking agent, was evaluated in 20 hyperthyroid patients. The patients improved to the same extent on either drug, as shown by a clinical diagnostic index. Basal metabolic rate decreased by 11% during both treatments, while it was unchanged in seven untreated hyperthyroid controls. Thyroxine concentration did not change during any treatment. During propranolol treatment T3 decreased from 4.6 to 3.9 nmol/l, while no changes were observed during atenolol treatment or in the control group. No significant changes were seen in free T4, free T3 or rT3 concentrations on any treatment, although free T3 was observed to decrease slightly during propranolol treatment. Thus, the improvement of the clinical symptoms of hyperthyroidism cannot be explained by diminished thyroid hormone concentrations in serum, since the reduction was small during propranolol and absent during atenolol treatment.

Adolescent↗
PubMed1981

Blood pressure and pulse response to insulin-induced hypoglycemia during non-selective and selective beta-blockade.

Hypoglycemia was induced in ten healthy male volunteers during medication with atenolol, metoprolol and propranolol. The beta-blockers abolished the tachycardia during hypoglycemia. In some subjects bradycardia, and in two nodal bradycardia was observed on propranol. The physiologic blood pressure responses were dampend during the beta1-selective blockade. With propranolol a rise in blood pressure was recorded, in two subjects up to 160/105. The blockers had no effect on degree of hypoglycemia or glucose recovery.

Adrenergic beta-Antagonists↗
PubMed1988

Selecting candidates for a medical school: an evaluation of a selection model based on cognitive and personality predictors.

Two studies were conducted to attempt to evaluate the selection procedures used in Hadassah Medical School. The predictors assessed were the Israeli high school matriculation examinations, a general aptitude test, an interview and a semi-projective test designed to assess personality pathology. In the first study 145 students of the 1975 and 1976 cohorts were assessed, the criteria being a combination of peer evaluations, evaluation of supervisors and academic record. Results showed the matriculation average score to be the only effective predictor for all criteria. In the second study 155 students of the 1979, 1980 and 1981 cohorts were assessed, the criteria being evaluation of supervising doctors, BSc grades and grades during the clinical period. Results again indicated that the matriculation test is the most effective predictor. In this study, however, the other variables added to the prediction of criteria based on clinical evaluations. The results were discussed, raising several possible explanations for the relatively high validity of the matriculation scores. It was suggested the matriculation scores capture personality dimensions, such as motivation and adjustment to the learning environment, which are important factors for success in medical training.

Aptitude Tests↗
PubMed1994

Substitution of aromatic and nonaromatic amino acids for the Phe3 residue in the delta-selective opioid peptide deltorphin I: effects on binding affinity and selectivity.

Deltorphins I and II (Tyr-D-Ala-Phe-Asp-Val-Val-Gly NH2 and Tyr-D-Ala-Phe-Glu-Val-Val-Gly NH2) display a high degree of delta-opioid receptor selectivity. Since they lack the intervening Gly3 residue found between the Tyr and Phe aromatic moieties in pentapeptide enkephalins, deltorphins I and II resemble a previously described series of cyclic tetrapeptides based on Tyr-c[D-Cys-Phe-D-Pen] (JOM-13). With the goal of development of structure-activity relationships for deltorphins and comparison with that of the cyclic tetrapeptides, ten analogs of deltorphin I were synthesized in which Phe3 was replaced with specific aromatic and nonaromatic amino acids with varying physicochemical properties. Results indicated that analogs containing the bicyclic aromatic amino acids 3-(1-naphthyl)-L-alanine [1-Nal; Ki(mu) = 767 nM, Ki(delta) = 7.70 nM], 3-(2-naphthyl)-L-alanine [2-Nal; Ki(mu) = 1910 nM, Ki(delta) = 49.2 nM], tryptophan [Ki(mu) = 1250 nM, Ki(delta) = 23.9 nM], and 3-(3-benzothienyl)-L-alanine [Bth; Ki(mu) = 112 nM, Ki(delta) = 3.36 nM] were fairly well tolerated at mu- and delta-receptors, though affinity was compromised to varying degrees relative to deltorphin I. Shortening the Phe side chain by incorporation of phenylglycine (Pgl) was detrimental to both mu (Ki = 4710 nM) and delta (Ki = 15.6 nM) binding, while extension of the side chain with homophenylalanine (Hfe) enhanced mu binding (Ki = 67.8 nM), leaving delta affinity unaffected (Ki = 2.64 nM). Substitution with nonaromatic amino acids valine and isoleucine led expectedly to poor opioid binding [Ki(mu) = > or = 10,000 nM for each, Ki(delta) = 160 and 94.7 nM, respectively], while peptides containing cyclohexylalanine (Cha) and leucine surprisingly retained affinity at both mu (Ki = 322 and 1240 nM, respectively) and delta (Ki = 10.5 and 12.4 nM, respectively) sites. In general, these trends mirror those observed for similar modification in Tyr-c[D-Cys-Phe-D-Pen].

Amino Acid Sequence↗
PubMed1991

ICI D7114 a novel selective beta-adrenoceptor agonist selectively stimulates brown fat and increases whole-body oxygen consumption.

1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosphate (GDP)-binding (ED50, 0.15 mg kg-1, p.o.) with no chronotropic effects on the heart at these doses. 2. Reference beta-adrenoceptor agonists, isoprenaline and clenbuterol, also stimulated oxygen consumption and BAT activity but were less selective because they also produced effects on heart rate at these doses. 3. Treatment of conscious rats with ICI D7114 did not attenuate the chronotropic effects on the heart of a subsequent isoprenaline challenge. 4. Administration of ICI D7114 or of its acid metabolite had no effect in a cat soleus muscle model of tremor or on blood potassium levels in the conscious dog, indicating lack of effects at beta 2-adrenoceptors. 5. The results indicate that ICI D7114 may have activity at atypical beta-adrenoceptors in brown adipose tissue leading to increased whole body oxygen consumption.

Adipose Tissue, Brown↗
PubMed1983

Failure to induce selective cholestasis in the rat after long-term extrahepatic selective biliary obstruction.

Forty-eight hours after extra-hepatic selective biliary obstruction (SBO), there is evidence of cholestasis in the obstructed lobes (OL). However, some major ultrastructural features of cholestasis are missing. The aim of this work was to investigate the long-term effect of SBO. One month after surgery, and in comparison with sham-operated rats, bile flow, liver weight, and liver weight ratio of obstructed/nonobstructed lobes were normal. Furthermore, there was no evidence of cholestasis in OL by light and electron microscopy. Bile duct communications between obstructed and non-obstructed lobes were evidenced by Indian ink injection. In sham-operated rats, bile duct communications between ducts of the different lobes were involved in bile drainage. It appears, therefore, that the main reason for the lack of cholestasis 1 month after SBO is the drainage of bile from OL through accessory bile ducts.

Animals↗
PubMed1977

Selective and non-selective beta-blockade in renin release.

The effects of two beta-adrenergic receptor blocking drugs, the non-selective propranolol and the beta1selective metoprolol, were studied on hemodynamics and plasma renin activity (PRA) of healthy volunteers in an ergometric exercise test. Oral doses of 160 mg of propranolol and 200 mg of metoprolol were tested against placebo. The drug plasma concentrations were determined. Heart rate and systolic blood pressure were equal and significantly lower during treatment with both active drugs when compared to placebo. The effect of drugs on exercise heart rate was correlated with the logarithm of drug plasma concentration with both propranolol and metoprolol. Propranolol, but not metoprolol, decreased the basal level of PRA. The ergometric exercise induced a significant rise in PRA after placebo but this increase was partially inhibited by the both active drugs. On the basis of these findings it is suggested that in man the basal level of PRA could be decreased mainly by blocking the beta2-adrenoceptors. Instead the exercise induced increase of PRA could be inhibited by blocking the beta1-adrenergic receptors.

Administration, Oral↗
PubMed1975

Selective and non-selective reinnervation of fast-twitch and slow-twitch rat skeletal muscle.

1. The problem of selectivity during reinnervation of skeletal muscle fibres was investigated in the rat using the fast-twitch extensor digitorum longus (EDL) and the slow-twitch soleus muscles and their nerves. 2. After an operation on these nerves permitting them to compete for reinnervation of one or the other muscle (hereafter called Y-union), virtually the total isometric tetanic tension of EDL muscle could be elicited by stimulating the EDL nerve, while stimulating the soleus nerve yielded little or no tension. In the case of the soleus muscle, stimulation of either nerve elicited about half of the total isometric tetanic tension. 3. During the course of reinnervation of these muscles in non-competitive situations, the time course of increase in the ratio of tension elicited by nerve stimulation to that by direct stimulation was slower in the case of soleus nerve reinnervating EDL muscle, compared with cross-reinnervation in the reverse direction or reinnervation of each muscle by its own nerve. 4. Crushing the common peroneal nerve 12 days after a Y-union in an attempt to retard the EDL nerve did not favour reinnervation of the EDL by soleus nerve, but crushing the nerve again or just once at 1 month after the original operation produced substantial partial reinnervation of the EDL by the soleus nerve. 5. It is concluded that soleus nerve fibres form functioning neuromuscular synapses on EDL muscle fibres only with difficulty. The pattern of reinnervation reveals characteristic differences between fast-twitch and slow-twitch muscles on the one hand and between their respective nerves on the other.

Animals↗
PubMed1999

Different vasoactive intestinal polypeptide receptor domains are involved in the selective recognition of two VPAC(2)-selective ligands.

A vasoactive intestinal polypeptide (VIP) analog, acylated on the amino-terminal histidine by hexanoic acid (C(6)-VIP), behaved as a VPAC(2) preferring agonist in binding and functional studies on human VIP receptors, and radioiodinated C(6)-VIP was a suitable ligand for binding studies on wild-type and chimeric receptors. We evaluated the properties of C(6)-VIP, its analog AcHis(1)-VIP, and the VPAC(2)-selective agonist Ro 25-1553 on the wild-type VPAC(1) and VPAC(2) receptors and on the chimeric receptors exchanging the different domains between both receptors. VIP had a normal affinity and efficacy on the chimeras starting with the amino-terminal VPAC(2) receptor sequence. The binding and functional profile of these chimeric receptors suggested that the high affinity of Ro 25-1553 for VPAC(2) receptors is supported by the amino-terminal extracellular domain, whereas the ability to prefer C(6)-VIP over VIP is supported by the VPAC(2) fifth transmembrane (TM5)-EC(3) receptor domain. These results further support the hypothesis that the central and carboxyl-terminal regions of the peptide (modified in RO 25-1553) recognize the extracellular amino-terminal region domain, whereas the amino-terminal VIP amino acids bind to the TM receptor core. VIP had a reduced affinity and efficacy on the N-VPAC(1)/VPAC(2) and on the N-->EC(2)-VPAC(1)/VPAC(2) chimeric receptors. C(6)-VIP behaved as a high-affinity agonist on these constructions. The antagonists [AcHis(1),D-Phe(2),Lys(15),Arg(16), Leu(27)]VIP(3-7)/GRF(8-27) and VIP(5-27) had comparable affinities for the wild-type receptors and for the two latter chimeras, supporting the hypothesis that these chimeras were properly folded but unable to reach the high-agonist-affinity, active receptor conformation in response to VIP binding.

Animals↗