Synthesis, NMR studies and conformational analysis of oxazolidine derivatives of the beta-adrenoreceptor antagonists metoprolol, atenolol and timolol

Formaldehyde-derived oxazolidine derivatives 4-7 of the beta-adrenoreceptor antagonists metoprolol 1, atenolol 2 and timolol 3 have been synthesised. Conformational analysis of 1-3 and the oxazolidine derivatives 4-7 has been performed using H-1 NMR spectroscopy and computational methods. The H-1 NMR studies show that for the aryloxypropanolamine beta-adrenoreceptor antagonists there is a predominance of the conformer in which the amine group is approximately antiperiplanar or trans to the aryloxymethylene group. Both H-1 NMR data and theoretical studies indicate that the oxazolidine derivatives 4-7 and the aryloxypropanolamine beta-adrenoreceptor antagonists 1-3 adopt similar conformations around the beta-amino alcohol moiety. Thus, oxazolidine ring formation does not dramatically alter the preferred conformation adopted by the beta-amino alcohol moiety of 1-3. Oxazolidine derivatives of aryloxypropanolamine beta-adrenoreceptor antagonists may therefore be appropriate as prodrugs, or semi-rigid analogues, when greater lipophilicity is required for drug delivery.

Analysis of immunosuppressive proteins in serum of liver-transplanted rats by using an anti-LSF-1 affinity column

Liver suppressor factor one (LSF-1) is a 40-kDa immunosuppressive protein in the serum of rats 60 days after orthotopic liver transplantation (OLT) between the nonrejector combination of DA donors into PVG; recipients. In the present study, the purification of proteins from rat OLT serum taken 60 days after transplantation Mras performed by affinity chromatography using the anti-LSF-1 polyclonal antibody (pAb). The assessment of column eluates using anti-LSF-1 and OLT serum was studied using rat heart and liver transplantation models. Rejection was not suppressed by the administration of OLT serum in heart or liver allografts. However, heart allografts treated with peak eluates (450 mu g single shot im, dissolved in Intralipos) taken from the affinity OLT serum survived significantly longer than untreated rats (median = 36.5 days; n = 7 vs 6.5 days; n = 5, respectively, P = 0.011). The same treatment with anti-LSF-1 column eluates also prolonged liver allografts significantly (>200 days) than those in either the untreated group (median = 11 days; n = 7) or those which received only Intralipos (median = 10.5 days; n = 5, P = 0.019). Subsequent analysis of the N-terminal sequences of some of the proteins which were eluted from the affinity column revealed that the homology of a 30-kDa protein was identical to hemoglobin alpha-chain, a 59-kDa protein to granulocyte inhibitory factor, a 70-kDa and a 90-kDa to albumin and its precursor, respectively. Although the specific immunosuppressive component has not been isolated, our results suggested that the anti-LSF-1 column can extract immunosuppressive moiety of LSF-1 from OLT serum. (C) 1998 Academic Press.

Development and standardization of the Self-regulation Skills Interview (SRSI): A new clinical assessment tool for acquired brain injury

The Self-regulation Skills Interview (SRSI) is a clinical tool designed to measure a range of metacognitive skills essential for rehabilitation planning, monitoring an individual's progress, and evaluating the outcome of treatment interventions. The results of the present study indicated that the SRSI has sound interrater reliability and test-retest reliability. A principle components analysis revealed three SRSI factors: Awareness, Readiness to Change, and Strategy Behavior. A comparison between a group of 61 participants with acquired brain injury (ABI) and a group of 43 non-brain-injured participants indicated that the participants with ABI had significantly lower levels of Awareness and Strategy Behavior, but that level of Readiness to Change was not significantly different between the two groups. The significant relationship observed between the SRSI factors and measures of neuropsychological functioning confirmed the concurrent validity of the scale and supports the value of the SRSI for post-acute assessment.

Self-awareness and psychosocial functioning following acquired brain injury: An evaluation of a group support programme

This study investigated a group support programme designed to improve self-awareness deficits and psychosocial functioning in a group of chronic patients (N = 21) with acquired brain injury (ABI). The participants were on average 8.6 years (range: 1-36 years) post-injury and were seen at the Brain Injury Association of Queensland, Australia. The assessment of participants involved two standardised measures of intellectual self-awareness with collateral reports from relatives. The present study introduced a new measure called the Self-Regulation Skills Interview (SRSI) which assessed higher levels of self awareness and self-regulation skills. Psychosocial functioning was assessed using a standardised self-report measure. At baseline the group had a relatively high level of intellectual self-awareness regarding their deficits, a low to moderate level of self-regulation skills, and significant psychosocial impairment. The participants were involved in a 16-week group programme which involved components of cognitive rehabilitation, cognitive-behavioural therapy, and social skills training. A post-intervention assessment indicated that participants had significantly improved levels of self-regulation skills and psychosocial functioning. A 6-month follow-up assessment indicated that overall, participants had maintained the gains made during the programme. The important role of self-regulation skills is emphasised as the principle factor contributing to the maintenance of the gains observed.

Dendrite coherency of Al-Si-Cu alloys

The dendrite coherency point of Al-Si-Cu alloys was determined by thermal analysis and rheological measurement methods by performing parallel measurements at two cooling rates for aluminum alloys across a wide range of silicon and copper contents. Contrary to previous findings, the two methods yield significantly different values for the fraction solid at the dendrite coherency point. This disparity is greatest for alloys of low solute concentration. The results from this study also contradict previously reported tl ends in the effect of cooling rate on the dendritic coherency point. Consideration of the results shows that thermal analysis is not a valid technique for the measurement of coherency. Analysis of the results from rheological testing indicates that silicon concentration has a dominant effect on grain size and dendritic morphology, independent of cooling rate and copper content, and thus is the factor that determines the fraction solid at dendrite coherency for Al-Si-Cu alloys.

Phylogenetic relationships and uncertain taxonomy of Pedomicrobium species

The phylogenetic relationships among the species of the genus Pedomicrobium were studied by comparing their 16S rRNA sequences, The Pedomicrobium species form a coherent phylogenetic cluster within the genera of the hyphal budding bacteria in the alpha-Proteobacteria. The sequences of two strains of Pedomicrobium australicum were obtained from DNAs extracted from nonviable freeze-dried cells, which are the only source of material available, and were found to be almost identical (level of similarity, 99.9%), Overall, the Pedomicrobium species are closely related, with sequence similarities ranging from 96.2 to 99.9%, Pedomicrobium manganicum is phylogenetically the most distantly related species and exhibits the lowest similarity (96.2%) with Pedomicrobium americanum, Australian isolate Pedomicrobium sp, strain ACM 3067, P, americanum, and P, australicum are all very highly related, with similarities greater than 99%, Pedomicrobium sp, strain ACM 3067 is most closely related to P, australicum (level of similarity, 99.6%) and P, americanum (99.4%), These manganese-oxidizing species are more closely related to the iron-oxidizing species Pedomicrobium ferrugineum than to the other manganese-oxidizing species, P, manganicum. Taxonomic uncertainties resulting from the loss of the type culture of P, australicum are discussed.

Evaluation of bioelectrical impedance for prospective nutritional assessment in cystic fibrosis

We have compared the use of bioelectrical impedance analysis (BIA) with anthropometry for the prediction of changes in total body potassium (TBK) in a group (n = 31) of children with cystic fibrosis. Linear regression analysis showed that TBK was highly correlated (r > 0.93) with height(2)/impedance, weight, height, and fat-free mass (FFM) estimated from skin-fold measurements. Changes in TBK were also correlated, but less well, with changes in height(2)/impedance, weight, height, and FFM (r = 0.69, 0.59, 0.44, and 0.40, respectively). The children were divided into two groups: those who had normal accretion of TBK (> 5%/y) and those who had suboptimal accretion of TBK (< 5%/y). Analysis of variance showed that the significant difference in the change in TBK between the groups was detectable by concomitant changes in impedance and weight but not by changes in height, FFM, or weight and height Z scores. The results of this study suggest that serial BIA measures may be useful as a predictor of progressive undernutrition and poor growth in children with cystic fibrosis. (C) Elsevier Science Inc. 1997.

Transformational leadership, corporate cultism and the spirituality paradigm: An unholy trinity in the workplace?

Leadership is a perennially popular topic in the academic and practitioner literature on management. In particular, the past twenty years have witnessed an explosive growth of interest in what has been termed 'transformational leadership' (henceforth, TL). The theory is closely linked to the growth in what has been defined as corporate culturism - an emphasis on the importance of cohereat cultures, as a means of securing competitive advantage. This article outlines the central components of TL theory, and subjects the concept to a critical analysis. In particular, similarities are identified between the components concerned and the characteristics of leadership practice in organizations generally defined as cults. This connection has been previously unremarked in the literature. These similarities are comprehensively reviewed. Trends towards what can be defined as corporate cultism in modem management practice are also discussed. We conclude that TL models are overly concerned with the achievement of corporate cohesion to the detriment of internal dissent Such dissent is a vital ingredient of effective decision-making. It is suggested that more inclusive and participatory models of the leadership process are required.

Comparative analysis of genetic diversity in the mangrove species Avicennia marina (Forsk.) Vierh. (Avicenniaceae) detected by AFLPs and SSRs

Avicennia marina is an important mangrove species with a wide geographical and climatic distribution which suggests that large amounts of genetic diversity are available for conservation and breeding programs. In this study we compare the informativeness of AFLPs and SSRs for assessing genetic diversity within and among individuals, populations and subspecies of A. marina in Australia. Our comparison utilized three SSR loci and three AFLP primer sets that were known to be polymorphic, and could be run in a single analysis on a capillary electrophoresis system, using different-colored fluorescent dyes. A total of 120 individuals representing six populations and three subspecies were samplcd. At the locus level, SSRs were considerably more variable than AFLPs, with a total of 52 alleles and an average heterozygosity of 0.78. Average heterozygosity for AFLPs was 0.193, but all of the 918 bands scored were polymorphic. Thus, AFLPs were considerably more efficient at revealing polymorphic loci than SSRs despite lower average heterozygosities. SSRs detected more genetic differentiation between populations (19 vs 9%) and subspecies (35 vs 11%) than AFLPs. Principal co-ordinate analysis revealed congruent patterns of genetic relationships at the individual, population and subspecific levels for both data sets. Mantel testing confirmed congruence between AFLP and SSR genetic distances among, but not within, population comparisons, indicating that the markers were segregating inde- pendently but that evolutionary groups (populations and subspecies) were similar. Three genetic criteria of importance for defining priorities for ex situ collections or in situ conservation programs (number of alleles, number of locally common alleles and number of private alleles) were correlated between the AFLP and SSR data sets. The congruence between AFLP and SSR data sets suggest that either method, or a combination, is applicable to expanded genetic studies of mangroves. The codominant nature of SSRs makes them ideal for further population-based investigations, such as mating-system analyses, for which the dominant AFLP markers are less well suited. AFLPs may be particularly useful for monitoring propagation programs and identifying duplicates within collections, since a single PCR assay can reveal many loci at once.

Applications of accurate, high-precision Pb isotope ratio measurement by multi-collector ICP-MS

The isotope composition of Ph is difficult to determine accurately due to the lack of a stable normalisation ratio. Double and triple-spike addition techniques provide one solution and presently yield the most accurate measurements. A number of recent studies have claimed that improved accuracy and precision could also be achieved by multi-collector ICP-MS (MC-ICP-MS) Pb-isotope analysis using the addition of Tl of known isotope composition to Pb samples. In this paper, we verify whether the known isotope composition of Tl can be used for correction of mass discrimination of Pb with an extensive dataset for the NIST standard SRM 981, comparison of MC-ICP-MS with TIMS data, and comparison with three isochrons from different geological environments. When all our NIST SRM 981 data are normalised with one constant Tl-205/Tl-203 of 2.38869, the following averages and reproducibilities were obtained: Pb-207/Pb-206=0.91461+/-18; Pb-208/Ph-206 = 2.1674+/-7; and (PbPh)-Pb-206-Ph-204 = 16.941+/-6. These two sigma standard deviations of the mean correspond to 149, 330, and 374 ppm, respectively. Accuracies relative to triple-spike values are 149, 157, and 52 ppm, respectively, and thus well within uncertainties. The largest component of the uncertainties stems from the Ph data alone and is not caused by differential mass discrimination behaviour of Ph and Tl. In routine operation, variation of sample introduction memory and production of isobaric molecular interferences in the spectrometer's collision cell currently appear to be the ultimate limitation to better reproducibility. Comparative study of five different datasets from actual samples (bullets, international rock standards, carbonates, metamorphic minerals, and sulphide minerals) demonstrates that in most cases geological scatter of the sample exceeds the achieved analytical reproducibility. We observe good agreement between TIMS and MC-ICP-MS data for international rock standards but find that such comparison does not constitute the ultimate. test for the validity of the MC-ICP-MS technique. Two attempted isochrons resulted in geological scatter (in one case small) in excess of analytical reproducibility. However, in one case (leached Great Dyke sulphides) we obtained a true isochron (MSWD = 0.63) age of 2578.3 +/- 0.9 Ma, which is identical to and more precise than a recently published U-Pb zircon age (2579 3 Ma) for a Great Dyke websterite [Earth Planet. Sci. Lett. 180 (2000) 1-12]. Reproducibility of this age by means of an isochron we regard as a robust test of accuracy over a wide dynamic range. We show that reliable and accurate Pb-isotope data can be obtained by careful operation of second-generation MC-ICP magnetic sector mass spectrometers. (C) 2002 Elsevier Science B.V. All rights reserved.

Growth hormone receptor and insulin-like growth factor-I immunoreactivity in osteoclast-like cells during tooth eruption in the toothless (Osteopetrotic) rat following treatment with colony-stimulating factor-1

In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt. Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone resorption by osteoclasts, permits tooth eruption, and up-regulates the immunoreactivity of bone marrow mononuclear cells to growth hormone receptor (GHr) and insulin-like growth factor (IGF)-I. This study examined the distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin, adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats, following treatment with CSF-1. Osteoclast-like cells demonstrated a positive reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue, osteoclast-like cells were generally negative for GHr. There was no significant difference in the total number of TRAP, GHr, and IGF-I-positive osteoclast-like cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl rats. CSF-1 treatment of the tl/tl rat significantly increased the total number of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p < 0.05) and IGF-I (P < 0.01).

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography - A comparison with contrast-enhanced magnetic resonance imaging

OBJECTIVES We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, 75% of the wall thickness replaced by scar. RESULTS As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (50% were viable by SPECT. CONCLUSIONS Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar. (C) 2004 by the American College of Cardiology Foundation.

Feeding strategies for grain-fed cattle in a hot environment

Six Bos taurus (Hereford) steers (body weight 324 22 kg) were used in a 45-day study with a replicated 3 x 3 Latin-square design. Three treatments [ad libitum feeding (ADLIB); limit feeding, 85% of ad libitum (LIMIT); bunk management feeding where steers were only given access to feed from 1600 to 0800 hours the following day (BUNK)] were imposed over 3 periods, with 2 steers assigned to each treatment in each period. Cattle were managed in a temperature-controlled metabolism unit and were exposed to both thermoneutral (17.7degreesC-26.1degreesC) and hot (16.7degreesC-32.9degreesC) environmental conditions. By design, during the thermoneutral period, the ADLIB cattle displayed greater intake (P < 0.05) than the LIMIT group, with the BUNK group being intermediate. However, during the hot period, both the LIMIT and BUNK treatment groups increased feed intake 4-5%, whereas feed intake of the ADLIB treatment group declined nearly 2%. During both periods respiration rate (RR, breath/min) followed the same pattern that was observed for feed intake, with the greatest (P < 0.05) RR found in the ADLIB treatment group (81.09 and 109.55, thermoneutral and hot, respectively) and lowest (P < 0.05) RR in the LIMIT treatment group (74.47 and 102.76, thermoneutral and hot, respectively). Rectal temperature (RT) did not differ among treatments during the thermoneutral period or the first hot day, although during the thermoneutral period the ADLIB treatment group did tend to display a lower RT, possibly as a result of other physiological processes (pulse rate and RR) aiding to keep RT lower. During the hot period, differences in RT were found on Day 5, with the LIMIT cattle having lower (P < 0.10) RT (38.92degreesC) than the ADLIB (39.18degreesC) cattle, with BUNK cattle RT (39.14degreesC) being intermediate. However, when hourly data were examined, the ADLIB cattle had greater(P < 0.05) RT than the BUNK and LIMIT at 1800 hours and greater RT (P < 0.05) than the LIMIT group at 1400, 1500, and 1600 hours. Clearly, a change in diurnal RT pattern was obtained by using the LIMIT and BUNK feeding regimen. Both of these groups displayed a peak RT during the hot conditions, between 2100 and 2200 hours, whereas the ADLIB group displayed a peak RT between 1400 and 1500 hours, a time very close to when peak climatic stress occurs. Based on these results it is apparent that feedlot managers could alleviate the effects of adverse hot weather on cattle by utilising either a limit-feeding regimen or altering bunk management practices to prevent feed from being consumed several hours prior to the hottest portion of the day.