Iron self diffusion in liquid pure iron and iron-carbon alloys.

With incoherent quasielastic neutron scattering self-diffusion coefficients [Formula: see text] in pure iron, and iron-carbon alloys containing 8.7 at% and 16.9 at% carbon have been measured. At the melting point [Formula: see text] in liquid iron is [Formula: see text] m2 s-1. For the close-to-eutectic Fe83.1C16.9 composition [Formula: see text] m2 s-1 at T[Formula: see text] K. Contradicting conclusions drawn from literature values of tracer diffusion experiments the addition of carbon has only a minor effect on the iron mobility: at a given temperature the self-diffusion coefficient in Fe83.1C16.9 is only 10% larger than in liquid iron, although mixing has a drastic effect on liquidus temperature and phase behavior.

Domino [4 + 1]-annulation of α,ß-unsaturated δ-amino esters with Rh(II)-carbenoids ­ a new approach towards multi-functionalized N-aryl pyrrolidines.

Catalytic decomposition of diazomalonates and other diazoesters using Rh(II)- and Cu(II)-complexes in the presence of α,ß-unsaturated δ-(N-aryl)amino esters gives rise to the formation of multi-functionalized pyrrolidines with yields of up to 82%. The reaction apparently occurs as a domino process involving the initial N-ylide formation followed by intramolecular Michael addition to the conjugated system of amino esters to afford the pyrrolidine heterocycle. The whole process can also be classified as a [4 + 1]-annulation of the δ-amino α,ß-unsaturated ester with the carbenoid intermediate.

Synthesis of alpha-trifluoromethyl alpha-amino acids with aromatic, heteroaromatic and ferrocenyl subunits in the side chain.

5-Benzyloxy-4-trifluoromethyl-1,3-oxazoles, obtained from 5-fluoro-4-trifluoromethyloxazoles and benzyl alcohols, are capable for rearrangements. A 1,3 shift of a benzyl group is the key step of a new general route toward alpha-trifluoromethyl substituted aromatic and heteroaromatic amino acids, demonstrating that 5-fluoro-4-trifluoromethyl-1,3-oxazole is a synthetic Tfm-Gly equivalent. On reaction with benzpinacol partially fluorinated oxazoles are transformed into bis(trifluoromethyl) substituted 2,5-diamino adipic acid and N-benzoyl-2-benzhydryl-3,3,3-trifluoroalanine.

Domino reactions with fluorinated five-membered heterocycles. alpha-Trifluoromethyl alpha-amino acids with unsaturated side-chains.

Alpha-trifluoromethyl alpha-amino acids with unsaturated side-chains have been prepared from 5-fluoro-4-trifluoromethyloxazole and allyl, propargyl as well as terpene alcohols in a one-pot procedure.

Proven strategies to reduce cardiovascular mortality in hemodialysis patients.

BACKGROUND: In hemodialysis patients, left ventricular hypertrophy (LVH) correlates with mortality. The reason for LVH in uremics is multifactorial. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH. METHODS: In 230 ambulatory patients, including patients with coronary artery disease, diabetes, diastolic and systolic dysfunction, we continued optimized cardiac therapy (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-beta. The dose of epoetin-beta for maintaining target hemoglobin (Hb) was 68 +/- 23 IU/kg/week. Serial echocardiograms were recorded every 3-6 months. The mean observation period was 4.8 +/- 1.2 years. RESULTS: Mean Hb at baseline was 11.2 +/- 2.0 versus 14.1 +/- 1.4 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI: 159 +/- 50.4 vs. 130.2 +/- 42.7 g/m(2); p < 0.001). In a subgroup of 2/3 of the patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2; p < 0.001). CONCLUSION: Baseline LVMI (p < 0.001), Hb increase (p < 0.03), and triple cardiac therapy (p < 0.03) were significant and independent prognostic factors for a reduction in LVMI. The annual cardiovascular mortality was 5%. Even anemia correction from 12 to 14 g/dl results in further (p < 0.001) regression of LVMI.

Hexafluoroacetone as protecting and activating reagent: site-selective functionalization of iminodiacetic acid.

Hexafluoroacetone was applied as a bidentate protecting and activating agent for the syntheses of RGD-peptide mimetics starting from iminodiacetic acid in solution and on solid phase.

Clinical studies on the blockade of the renin-angiotensin-aldosterone-system.

The clinical value of inhibition of the renin-angiotensin-aldosterone-system (RAAS) in heart failure has clearly been documented for the ACE-inhibitors as well as for the angiotensin-I-receptor blocker (AT1) by extensive intervention studies (AIRE, CONSENSUS, SAVE, ELITE II, ValHeFT and others). The additional specific vascular and renal protection, acting beyond the lowering of blood pressure, has been investigated in the past years in numerous studies in patients with arterial hypertension, often accompanied by diabetes mellitus type II. Whereas for nephroprotection, especially also in additionally present diabetes mellitus type II, study results clearly support the assumption of additional protective effects, which exceed the purely blood-pressure lowering effect; the data available for vascular protection (coronary and cerebral vessels) are insufficient.

Clinical studies on the therapy of heart failure using ACE-inhibitors and AT1-receptor blockers--does combination treatment make sense?

In all industrial nations the number of patients with heart hailure is increasing. Pharmacological treatment with Angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalization in these patients. Inspite of these therapies, morbidity and mortality remains problematic. Possibly phenomena like the genetic induced Angiotensin-II-escape are responsible for the individual response in patients. Regarding their different pharmacological effects the new group of Angiotensin-II type 1 receptor (AT1) blockers seem to be promising for the treatment of heart failure. In trials like ELITE 1, ELITE 2 and Val-HeFT it could be demonstrated that AT1-blockers and ACE-inhibitors have a comparable effect in improving survival of heart failure patients. In the Val-HeFT study the combination of an ACE-inhibitor and an AT1-blocker reduce hospitalization and improve quality of life of heart failure patients compared with single treatment using an ACE-inhibitor or AT1-blocker. Mortality showed no significant difference. Before a final assessment of the combination treatment with ACE-inhibitors and AT1- blockers in heart failure patients we need more studies like the present CHARM-study.

Regression of left ventricular hypertrophy in hemodialysis patients is possible.

Regression of left ventricular hypertrophy in hemodialysis patients is possible. Left ventricular hypertrophy represents the major risk factor for cardiac morbidity and mortality. Therefore, their regression is mandatory. Since the causes of uremia-associated left ventricular hypertrophy are multifactorial, various therapeutic options can be considered: optimal control of arterial hypertension and volume status, optimal correction of metabolic acidosis, best possible correction of hypoalbuminemia and severe secondary hyperparathyroidism, modern pharmacotherapeutic strategy for the treatment of heart failure (use of angiotensin-converting enzyme inhibitors in combination with angiotensin II receptor blockers and beta-blockers) and total correction of renal anemia. Following the proposed therapeutic strategies we could, by using echocardiography, distinguish in 100 hemodialysis patients the following 3 groups (on the average after 1.5 years): 36 patients with initially normal left ventricular mass index (LVMI (g/m2), F < 110; M < 130) maintained normal (group 1); in 31 patients with moderately increased LVMI full regression resulted (group 2); 33 patients with severely increased LVMI (group 3) had to be further divided into 2 sub-groups: 22 patients with significant improvement of LVMI, 11 patients with no, regression. For the first time we were able to show that it is possible to maintain initially normal LVMI during long-term treatment and to achieve complete regression and significant improvement of LVMI in our patients. However, since LVMI requires a long time to develop, a similarly long time must be estimated for its regression. However, 11 patients remained therapeutically resistant. In this group, severe heart diseases were often combined and highly prevalent, including ischemic heart and valve diseases and end-stage dilatative cardiomyopathy. These patients had to be transferred to cardiac surgery. Anemia is considered to be one of the most important factors for the development of left ventricular hypertrophy. Therefore, total correction of renal anemia has to be strongly recommended in addition to other measures of our therapeutic strategy to maintain full or significant regression of left ventricular hypertrophy.

Glycoside carbamates from benzoxazolin-2(3H)-one detoxification in extracts and exudates of corn roots.

Zea mays was incubated with the natural phytotoxin benzoxazolin-2(3H)-one (BOA) to investigate the detoxification process. A hitherto unknown detoxification product, 1-(2-hydroxyphenylamino)-1-deoxy-beta-gentiobioside 1,2-carbamate (3), was isolated and identified. A reinvestigation of known BOA detoxification products by NMR methods led to the finding that the structure of benzoxazolin-2(3H)-one-N-beta-glucoside (1) first reported from Avena sativa has to be revised. In fact, the correct structure is that of the isomeric 1-(2-hydroxyphenylamino)-1-deoxy-beta-glucoside 1,2-carbamate 2, which is structurally related to 3. It was now shown with a synthetic mixture of 1 and 2 that 1 underwent spontaneous isomerization to form 2 in solution. Thus, N-glucosylation of BOA in the plant led finally to the carbamate 2. In contrast to BOA-6-O-glucosylation, BOA-induced N-glucosylation appears first after 6-8 h of incubation. As soon as N-glucosylation is possible, BOA-6-O-glucoside is not further accumulated, whereas the amount of glucoside carbamate increases continuously during the next 40 h. Synthesis of gentiobioside carbamate seems to be a late event in BOA detoxification. All detoxification products are released into the environment via root exudation.

Recombinant phytochrome A in yeast differs by its spectroscopic and photochemical properties from the major phyA' and is close to the minor phyA": evidence for posttranslational modification of the pigment in plants.

Previously, two pools of phytochrome A (phyA' and phyA") have been detected by in situ low-temperature fluorescence spectroscopy and photochemistry; it was suggested that they might differ in the nature of their posttranslational modification. In order to verify this possibility Arabidopsis and rice (Oryza) phyA were expressed in yeast and the pigments were assembled in vivo with phycocyanobilin (PCB) and phytochromobilin (P phi B). The resulting recombinant phytochromes in the red-light-absorbing form (Pr) were characterized in the yeast cell by (1) the fluorescence emission spectra; (2) the temperature dependence of Pr fluorescence intensity and activation energy of fluorescence decay; and (3) the extent of photoconversion of Pr into photoproduct lumi-R (gamma 1) or far-red-light absorbing form (Pfr) (gamma 2). Both Arabidopsis phyA/PCB and Oryza phyA/P phi B had low gamma 1 of ca 0.05, allowing their attribution to the Pr" phenomenological type of phytochrome comprising phyA", phyB and cryptogam phytochromes. The spectroscopic properties of Oryza phyA/P phi B were also very close to phyA". However, both investigated holoproteins differed from phyA", both with respect to the character of temperature dependence of the fluorescence yield and activation energy. Thus, recombinant Oryza phyA/P phi B is similar but not identical to phyA". The data demonstrate that the low-abundance-fraction plant phyA (phyA") comes from the same gene as the major (phyA') fraction. Because both endogenous phyA fractions differ from the phytochrome expressed in yeast, they appear to be posttranslationally modified and/or bound to partner proteins or cellular substructures. However, the character of the presumed chemical modification is different in phyA' and phyA" and its extent is more profound in the case of the former.

WinPep 2.11: novel software for PC-based analyses of amino acid sequences.

WinPep 2.11 is the latest version of a user-friendly, versatile software for the analysis of amino acid sequences. WinPep was developed for Windows 95/98 and WindowsNT. Because of the standard windows techniques (copy & paste) and an intuitive user interface, no lengthy training is required to work with this program. Main features include calculation of molecular weight, isoelectric point, and molar absorption coefficients, as well as simulation of sequence specific cleavage. In addition to data analysis, data presentation is greatly assisted by the program, e.g., by producing helical wheel displays and hydropathy plots. The implemented functions of WinPep and it's usage are described in this publication.

Negative interference of endogenous phytochrome B with phytochrome A function in Arabidopsis.

To study negative interactions between phytochromes, phytochrome B (phyB) overexpressor lines, the mutants phyA-201, phyB-4, phyB-5, phyD-1, phyA-201 phyB-5, phyA-201 phyD-1, and phyB-5 phyD-1 of Arabidopsis were used. Endogenous phyB, but not phytochrome D (phyD), partly suppressed phytochrome A (phyA)-dependent inhibition of hypocotyl elongation in far-red light (FR). Dichromatic irradiation demonstrated that the negative effect of phyB was largely independent of the photoequilibrium, i.e. far-red light absorbing form of phytochrome formation. Moreover, phyB-4, a mutant impaired in signal transduction, did not show a loss of inhibition of phyA by phyB. Overexpression of phyB, conversely, resulted in an enhanced inhibition of phyA function, even in the absence of supplementary carbohydrates. However, overexpression of a mutated phyB, which cannot incorporate the chromophore, had no detectable effect on phyA action. In addition to seedling growth, accumulation of anthocyanins in FR, another manifestation of the high irradiance response, was strongly influenced by phyB holoprotein. Induction of seed germination by FR, a very low fluence response, was suppressed by both endogenous phyB and phyD. In conclusion, we show that both classical response modes of phyA, high irradiance response, and very low fluence response are subject to an inhibitory action of phyB-like phytochromes. Possible mechanisms of the negative interference are discussed.

Both subunits of the dimeric plant photoreceptor phytochrome require chromophore for stability of the far-red light-absorbing form.

The dimeric plant photoreceptor phytochrome is converted from its inactive red light-absorbing form (Pr) into the active far-red light-absorbing form (Pfr) upon light absorption. Dynamics of Pfr generation and of thermal Pfr-to-Pr conversion are of fundamental importance for inducing adequate responses to light signals. Here, we analyzed the role of subunit interactions on spectroscopic properties of dimeric phytochrome A. Using a coexpression system and affinity chromatography, we prepared mixed phytochrome dimers that can incorporate the essential chromophore only in one subunit. We demonstrate that such mixed dimers have unaltered difference spectra. In contrast, dark reversion differed greatly between Pfr-Pfr homodimers and Pfr-Pr heterodimers, the former being about 100-fold more stable. Temperature dependence of reaction rates revealed an additional stabilization of about 4 kcal/mol in homodimers. Consequences of these findings are discussed in relation to the biological function of, and functional diversification between, phytochrome family members.

Designing and facilitating class discussion in an Internet class.

Designing a replacement for face-to-face classroom discussion is a major consideration in the development of an Internet course, whether the course is completely new or a redesign of an existing course. The experiences of four faculty members who were involved in developing courses for a baccalaureate completion program for RNs taught entirely on the Internet will be used to illustrate key issues in designing andfacilitating on-line discussion.

N-Glycosidation of D-arabino-hex-2-ulosonic acid.

Two approaches to N-functionalized D-arabino-hex-2-ulosonic acid derivatives were established by nucleophilic substitution of methyl (3,4,5-tri-O-acetyl-beta-D-arabino-hex-2-ulopyranosyl)onate bromide (1). Reaction of 1 with amino compounds in the presence of mercury(II) cyanide led to the 2,3-cis configured beta-D-arabino N-glycosides. On the other hand, the reaction of bromide 1 with azide, followed by catalytic hydrogenation led to 2,3-trans alpha-D-arabino glycosyl amine methyl 3,4,5-tri-O-acetyl-2-amino-alpha-D-arabino-hex-2-ulopyranosonate, which was easily rearranged to the thermodynamically more stable beta-D-arabino N-acetyl derivative methyl 4,5-di-O-acetyl-2-acetylamino-3-hydroxy-beta-D-arabino-hex-2-ulopyranosonate. The assignment of configuration of the tertiary anomeric centre and conformation of all products was based on 1H NMR H,H coupling constants and NOE difference experiments.

Caracterización de 50 mujeres jóvenes con cáncer de mama / Characterization of 50 young women with breast cancer

El cáncer mamario en mujeres jóvenes es frecuente, difícil de diagnosticar y motiva controversias si es más agresivo que el de las mujeres de mayor edad. Entre 1989 y 1998 estudiamos retrospectivamente 50 mujeres jóvenes tratadas por esta neoplasia maligna. El promedio de edad fue de 35,2 años (margen 24 a 40 años). La detección fue realizada por la paciente en 43 (86 por ciento) casos, en 7 (14 por ciento) por examen físico y en 2 (4 por ciento) por mamografía. El tamaño promedio clínico del tumor primario fue de 4,6 cm (margen 1 a 17 cm) y el tamaño anatomopatológico fue de 3,79 cm (margen 1 a 15 cm). La axila fue clínicamente positiva en 22 (44 por ciento) pacientes e histológicamente positiva en 27 (55, 1 por ciento) de 49 casos evaluados. En 3 (6 por ciento) casos se encontró diseminación sistémica. De 44 mamografías realizadas, 29 (65,9 por ciento) sugirieron cáncer y las 32 citologías practicadas resultaron positivas. La estadificación correspondió en 7 (14 por ciento) casos al estadio I, 24 (48 por ciento) al II 16 (32 por ciento) al III y 3 (6 por ciento) al IV. Se realizó cirugía conservadora en 18 (34,6 por ciento) casos, mastectomía radical en 16 (30,8 por ciento) y simple extendida en 13 (25 por ciento). El estudio histológico de 49 casos reveló en 39 (79,5 por ciento) carcinoma canalicular; el grado histológico evaluado en 43 casos fue II en 19 (44,1 por ciento) y III en 20 (46,5 por ciento) y el grado nuclear de los mismos 43 pacientes fue 2 en 17 (39,5 por ciento) casos y I en 23 (53,4 por ciento). Con seguimiento promedio de 46 meses (margen 6 a 120 meses) 28 (56 por ciento) pacientes se encuentran vivas sin evidencias de enfermedad, 3 (6 por ciento) vivas con enfermedad y 19 (38 por ciento) han fallecido. Las características sobresalientes de las pacientes estudiadas fueron: detección de primario voluminoso, alto rendimiento diagnóstico de la citología para confirmar diagnóstico, e histológicamente tumores moderadamente o mal diferenciados y grados nucleares medianos o altos

Some selective reactions of moenomycin A.

A number of new moenomycin A derivatives have been prepared. Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

Isolation, identification, and synthesis of gamma-butyrobetainyl-CoA and crotonobetainyl-CoA, compounds involved in carnitine metabolism of E. coli.

A still unknown low-molecular-mass cofactor essential for the activity of carnitine-metabolizing enzymes (e.g., L-carnitine dehydratase, crotonobetaine reductase) from E. coli has been purified to homogeneity from a cell-free extract of E. coli O44K74. The purity of the cofactor was confirmed by HPLC analysis. Biosynthesis of the unknown compound was only observed when bacteria were cultivated anaerobically in the presence of L-carnitine or crotonobetaine. The determined properties, together with results obtained from UV-visible, (1)H NMR, and mass spectrometry, indicate that the compound in question is a new CoA derivative. The esterified compound was suggested to be gamma-butyrobetaine-a metabolite of carnitine metabolism of E. coli. Proof of structure was performed by chemical synthesis. Besides gamma-butyrobetainyl-CoA, a second new CoA derivative, crotonobetainyl-CoA, was also chemically synthesized. Both CoA derivatives were purified and their structures confirmed using NMR and mass spectrometry. Comparisons of structural data and of the chemical properties of gamma-butyrobetainyl-CoA, crotonobetainyl-CoA, and the isolated cofactor verified that the unknown compound is gamma-butyrobetainyl-CoA. The physical and chemical properties of gamma-butyrobetainyl-CoA and crotonobetainyl-CoA are similar to known CoA derivatives.

Cardiac mortality prevention in uremic patients. Therapeutic strategies with particular attention to complete correction of renal anemia.

BACKGROUND: Left ventricular hypertrophy represents the major risk factor for cardiac mortality and morbidity, with cardiac mortality being the most important determinant for survival in dialysis patients. The prevalence of left ventricular hypertrophy is already high at initiation of dialysis and increases with time. Anemia is considered as the most important factor for the development of left ventricular hypertrophy. Others already demonstrated that with partial correction of renal anemia by erythropoietin a partial regression of the left ventricular mass can be achieved. PATIENTS AND METHODS: We investigated the effect of complete correction of renal anemia to normal hemoglobin values of 14 g/dl (Hct 42%) on left ventricular hypertrophy by echocardiography. Eight Patients entered the study 4-8 weeks after initiation of chronic hemodialysis with a mean hemoglobin of 9.5 +/- 1.3 g/dl). RESULTS: Left ventricular mass index (LVMI) decreased from 155 +/- 45 g/m2 to 123 +/- 18g/m2 (p < 0.05) within the observation period of 12 +/- 5 months. The results showed, that either normal left ventricular dimensions could be preserved or, if left ventricular hypertrophy was already present, complete regression was possible. CONCLUSION: Therefore, we propose that complete correction of renal anemia should be introduced into the therapy of dialysis patients along with strict adherence to established measures for the control of left ventricular hypertrophy: control of fluid overload and arterial hypertension and the use of ACE-inhibitors and betablockers. In addition, optimal correction of metabolic acidosis, control of the calcium-phosphate product and hyperparathyreoidism must be attempted. Thus, it should be possible to reverse left ventricular hypertrophy and its deleterious consequences in the dialysis population in order to improve survival and quality of life.