Quantitative first-principles calculations of valence and core excitation spectra of solid C60.

We present calculated valence and C 1s near-edge excitation spectra of solid C60 and experimental results measured with high-resolution electron energy-loss spectroscopy. The near-edge calculations are carried out using three different methods: solution of the Bethe-Salpeter equation (BSE) as implemented in the OCEAN suite (Obtaining Core Excitations with ab initio methods and the NIST BSE solver), the excited-electron core-hole approach (XCH), and the constrained-occupancy method using the Stockholm-Berlin core-excitation code, StoBe. The three methods give similar results and are in good agreement with experiment, though the BSE results are the most accurate. The BSE formalism is also used to carry out valence level calculations using the NIST Bethe-Salpeter Equation solver (NBSE). Theoretical results include self-energy corrections to the band gap and band widths, lifetime-damping effects, and Debye-Waller effects in the core-excitation case. A comparison of spectral features to those observed experimentally illustrates the sensitivity of certain features to computational details, such as self-energy corrections to the band structure and core-hole screening.

Chemistry of free radicals produced by oxidation of endogenous α-aminoketones. A study of 5-aminolevulinic acid and α-aminoacetone by fast kinetics spectroscopy.

BACKGROUND: Excess 5-aminolevulinic acid (ALA) and α-aminoacetone (AA) are implicated in ketosis, porphyrinpathies and diabetes. Pathologic manifestations involve O2⁻, H2O2, OH, enoyl radicals (ALA and AA) and their oxidation end products. METHODS: To characterize enoyl radicals resulting from reaction of OH radicals with ALA and AA, micromolar OH concentrations were produced by pulse radiolysis of ALA and AA in aqueous solutions. RESULTS: ALA and AA react with OH at k=1.5 × 109 M⁻¹s⁻¹. At pH7.4, the ALA absorbance spectrum has a maximum at 330 nm (ε=750 M⁻¹cm⁻¹). This band appears as a shoulder at pH8.3 where two ALA species are present: (NH3)⁺-CH2-CO-CH2-CH2-COO⁻ and NH2-CH2-CO-CH2-CH2-COO⁻ (pKa=8.3). At pH8.3, ALA reacts with oxygen (k=1.4 × 108 M⁻¹s⁻¹) but not with O2⁻. At pH8.3, AA oxidation produces two AA species characterized by an absorbance spectrum with maxima at 330 and 450 nm. ALA and AA are repaired by antioxidants (quercetin (QH), catechin, trolox, ascorbate) which are semi-oxidized (k>10(8)M⁻¹s⁻¹). QH bound to HSA or to apoferritin and ferritin repairs ALA and AA. In O2-saturated apoferritin solutions, Q, O2⁻, AA and reaction product(s) react with QH. CONCLUSIONS: The optical absorption properties and the time evolution of ALA and AA were established for the first time. These radicals and their reaction products may be neutralized by antioxidants free in solution or bound to proteins. GENERAL SIGNIFICANCE: Adjuvant antioxidant administration may be of interest in pathologies related to excess ALA or AA production.

Synthesis of highly nitrogen-doped multi-walled carbon nanotubes.

We present a new synthesis route for nitrogen doped carbon nanotubes (CNx) based on the aerosol method. Tubes with a record high concentration of nitrogen (approximately 20 atom%) have been synthesized, confirmed by electron energy loss spectroscopy (EELS). A strong correlation between the N/C ratio and morphology of the tubes is observed and discussed.

Redox reactions of the urate radical/urate couple with the superoxide radical anion, the tryptophan neutral radical and selected flavonoids in neutral aqueous solutions.

The kinetics of several processes involving the potential antioxidant role of urate in physiological systems have been investigated by pulse radiolysis. While the monoanionic urate radical, .UH-, can be produced directly by oxidation with .Br2- or .OH, it can also be generated by oxidation with the neutral tryptophan radical, .Trp, with a rate constant of 2 x 10(7) M-1s-1. This radical, .UH-, reacts with .O2- with a rate constant of 8 x 10(8) M-1s-1. Also, .UH- is reduced by flavonoids, quercetin and rutin in CTAB micelles at rate constants of 6 x 10(6) M-1s-1 and 1 x 10(6) M-1s-1, respectively. These results can be of value by providing reference data useful in further investigation of the antioxidant character of urate in more complex biological systems.

Study of the local atomic strain field in a Zr-doped TiAl intermetallic alloy by EXAFS and ab initio FLAPW calculations.

The mechanical properties of gamma-TiAl-based intermetallic alloys are strongly influenced by Ti d-Ti d and Al p-Ti d hybridizations. These directional bonds supply good mechanical properties at high temperature but they are also associated with a low ductility at room temperature. Small amounts (about 3%) of additional elements can improve this behaviour noticeably and modify the mechanical properties. In the present case, the addition of zirconium in the gamma-TiAl-based alloys has been reported to increase their ductility at low temperature. Beyond the modifications of the directional bonds which come directly from the band structure, the different atomic volumes of the solute atoms induce local deformation fields which interact with the dislocations. We present ab initio calculations (FLAPW method) compared with an EXAFS study which the aim is to determine the site preference of zirconium in the TiAl lattice and the deformation fields around the solute atoms.

Literature search improvement project.

This paper describes an ongoing improvement effort directed at increasing the quality of mediated searches at the Sladen Library and Center for Health Information Resources. The project is the result of an analysis of literature statistics for mediated searching for 1997. The improvement project utilizes Deming's Plan-Do-Check-Act or PDCA cycle. Henry Ford Health System encourages use of the PDCA methodology for improvement projects. A key component of this improvement effort was the introduction of a productivity standard that each searcher is required to meet. The library has global productivity goals, but this is the first time that individual searchers have been held to a quantitative performance standard. The outcome of the Literature Search Improvement Project has been favorable.

Interactions of superoxide anion with enzyme radicals: kinetics of reaction with lysozyme tryptophan radicals and corresponding effects on tyrosine electron transfer.

The kinetics of O2*- reaction with semi-oxidized tryptophan radicals in lysozyme, Trp*(Lyz) have been investigated at various pHs and conformational states by pulse radiolysis. The Trp*(Lyz) radicals were formed by Br2*- oxidation of the 3-4 exposed Trp residues in the protein. At pH lower than 6.2, the apparent bimolecular rate is about 2 x 10(8) M(-1) s(-1); but drops to 8 x 10(7) M(-1) s(-1) or less above pH 6.3 and in CTAC micelles. Similarly, the apparent bimolecular rate constant for the intermolecular Trp*(Lyz) + Trp*(Lyz) recombination reaction is about (4-7 x 10(6) M(-1) s(-1)) at/or below pH 6.2 then drops to 1.3-1.6 x 10(6) M(-1) s(-1) at higher pH or in micelles. This behavior suggests important conformational and/or microenvironmental rearrangement with pH, leading to less accessible semi-oxidized Trp* residues upon Br2*- reaction. The kinetics of Trp*(Lyz) with ascorbate, a reducing species rather larger than O2*- have been measured for comparison. The well-established long range intramolecular electron transfer from Tyr residues to Trp radicals--leading to the repair of the semi-oxidized Trp*(Lyz) and formation of the tyrosyl phenoxyl radical is inhibited by the Trp*(Lyz) + O2*- reaction, as is most of the Trp*(Lyz) + Trp*(Lyz) reaction. However, the kinetic behavior of Trp*(Lyz) suggests that not all oxidized Trp residues are involved in the intermolecular recombination or reaction with O2*-. As the kinetics are found to be quite pH sensitive, this study demonstrates the effect of the protein conformation on O2*- reactivity. To our knowledge, this is the first report on the kinetics of a protein-O2*- reaction not involving the detection of change in the redox state of a prosthetic group to probe the reactivity of the superoxide anion.

Photo-oxidation of methionine-containing peptides by the 4-carboxybenzophenone triplet state in aqueous solution. Competition between intramolecular two-centered three-electron bonded (S...S)+ and (S...N)+ formation.

Quantum yields for the formation of transients were measured following the quenching of triplet 4-carboxy-benzophenone (3CB*) by methionine-containing peptides in aqueous solutions. Ketyl radicals (CBH.), ketyl radical anions (CB.-) and various sulfur radical cations were identified following the triplet-quenching events. The presence of these intermediates indicated that the triplet-quenching mechanism can be characterized as mainly electron-transfer in nature. The quenching rate constants were of the order of 2 x 10(9) M-1 s-1. There were small, but significant, differences in the triplet-quenching rate constants, and these trends indicate the existence of multiple sulfur targets in the quenchers. The absorption of the transient products was followed in detail by using spectral-resolution analysis. From the absorption data, quantum yields were estimated for the formation of the various transients. There were differences found in the yields of the transient products between the experiments, where the quenchers were the "mixed" stereoisomers of methionylmethionine (L,D and D,L) and experiments where the quenchers were L,L and D,D stereoisomers. Triplet-quenching data from several other methionine-containing small oligopeptides were analyzed in an analogous manner. Systematic variations were observed, and these patterns were discussed in terms of competitive donation of protons to the CB.- within the charge-transfer complex. The competition was between protons on carbons adjacent to the sulfur-radical center and protons on the protonated amino groups of the radical cation. In addition, there was a competition between the two intramolecular two-centered, three-electron bonded species (S therefore S)+ and (S therefore N)+ that play roles in the secondary kinetics.

Liver transplantation for glycogen storage disease types I, III, and IV.

UNLABELLED: Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. CONCLUSION: Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form.

Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.

BACKGROUND: Genetic defects are being increasingly recognized in the etiology of primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. METHODS AND RESULTS: We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible.

Perceived hearing handicap of patients with unilateral or mild hearing loss.

Using the Hearing Handicap Inventory for Adults (HHIA), we assessed self-perceived hearing handicap in a sample of 63 patients having either unilaterally normal hearing or a mild hearing loss (pure tone average < or = 40 dB hearing level). Large intersubject variability in responses to the HHIA confirmed observations that reactions to minimal hearing impairment vary greatly among patients. The individual differences in responses highlight the importance of quantifying the perceived communication and psychosocial handicap, which cannot be determined from the audiogram alone. An item examination of responses to the HHIA revealed a number of emotional and social-situational problems encountered by patients with minimal hearing loss.

[Assisted dying and conflict of interest]. / Sterbehilfe und Interessenkonflikte.

A Swiss physician obtained his elderly patient's house, valued at $2 million, as a gift. The patient retained the right to stay in the house until her death. The physician also knew that she had made him the beneficiary of her estate, valued at + 10 million. She then died of untreated pneumonia while in his care. He had not discussed withholding of antibiotics with her or her family. In countries with advanced life-sustaining technology, 35% of all deaths are thought to occur after withholding of treatment. Physicians and others making such "MDEL" (medical decisions concerning the end of life) have a conflict of interest, if they benefit from their patients' death. These conflicts are unethical. They are dangerous to patients, physicians, the medical profession, and the public. The Netherlands have laws and rules of professional conduct that prohibit MDEL-for-profit, i.e., a mode of assisted dying that benefits caregivers to the detriment of patients and their families.

Effect of growth hormone on urine calcium and serum vitamin D metabolites in renal failure.

Growth hormone (GH) causes a modest increase in urine calcium excretion in normal adults, but uremic rats given both GH and calcitriol developed hypercalciuria. Ten short prepubertal children with renal insufficiency treated with recombinant human GH (rhGH) had urine calcium to creatinine (Ca/Cr) ratios and serum vitamin D metabolite concentrations monitored prospectively for up to 24 months. Six were also treated with calcitriol and two with other vitamin D preparations. Mean urine Ca/Cr ratios or mean serum concentrations of 1,25-dihydroxy vitamin D, 24,25-dihydroxy vitamin D, and 25-hydroxy vitamin D did not change significantly during treatment with rhGH. The risk for rhGH-induced hypercalciuria is small in children with renal insufficiency, even when treated concomitantly with a vitamin D preparation.

Biochemical and molecular analysis in a patient with the severe form of Hunter syndrome after bone marrow transplantation.

Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results from a deficiency of iduronate-2-sulfatase (IDS) activity due to a primary genetic defect in the X-chromosomal iduronate-2-sulfatase gene. We have studied a 10-year-old male, diagnosed with Hunter syndrome at age 2 years, who underwent bone marrow transplantation (BMT) at age 5 years. To evaluate the metabolic effect of BMT, biochemical and enzymatic studies were performed. Urinary glycosaminoglycans (GAGs) were quantitated, and iduronate-2-sulfatase activity was measured in serum, leukocytes, and liver homogenates. Decreased urinary glycosaminoglycan excretion and increased iduronate-2-sulfatase activity in serum and leukocytes were observed. Furthermore, molecular analysis was performed using reverse transcriptional polymerase chain reaction (RT-PCR) sequencing and restriction enzyme assay. The patient was found to have a novel nonsense mutation, L279X (TTA to TGA) in exon 6 of the IDS gene, inherited from his mother. A comparison of the DNA contents of cultured skin fibroblasts prior to BMT with leukocyte DNA after BMT showed coexisting host mutant and donor normal alleles in post-BMT leukocyte DNA. We postulate that the L279X mutation is a severe disease-causing mutation for Hunter syndrome.

Do neuron-specific enolase levels discriminate between small-cell lung cancer and mediastinal tumors?

The capacity of pretherapeutically assessed neuron-specific enolase (NSE) to differentiate between small cell lung cancer (SCLC) and mediastinal tumors was investigated retrospectively in a series of 320 patients. NSE was found to be increased in 95/130 (73.1%) patients with SCLC, in 4/62 (6.5%) patients with Hodgkin's disease, in 10/58 (17.2%) patients with non-Hodgkin's lymphoma, in 5/16 (31.3%) patients with teratoma, and in 6/54 (11.1%) patients with thymoma. The cut-off value, defined as the 95% percentile of a reference population suffering from benign pulmonary disorders (n = 192), was set at 13.8 ng/ml. When this discrimination level was increased to 26.4 ng/ml, which corresponds to a 95% specificity versus the total group with mediastinal tumors, SCLC was recognized with a detection rate of only 49.2%. In conclusion, increased NSE concentrations in a patient with a hilar mass and/or mediastinal widening on X-ray are not always diagnostic of SCLC due to the high rate of elevated NSE values associated with mediastinal tumors. However, in a patient who presents with a hilar mass and a high NSE level, bronchoscopy is always indicated to obtain adequate specimens for histology in order to plan an appropriate therapeutic regimen.

Weanling and adult rats differ in fatty acid and carnitine metabolism during sepsis.

Increased oxidation of fat is an important host response to sepsis, and carnitine is essential for long-chain fatty acid oxidation. Because neonates have low levels of carnitine, their ability to respond to a septic insult may be impaired. The purpose of this study was to compare fatty acid and carnitine metabolism in septic weanling (60 to 85 g) and septic adult (285 to 310 g) rats. Sepsis was induced in weanling and adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were killed 16 hours after CLP or sham operation, and serum glucose, lactate, beta-hydroxybutyrate, fatty acid, carnitine, liver fatty acid, and tissue carnitine levels were measured. The data suggest that during sepsis weanling rats may be more dependent on fatty acid oxidation than adult rats are, as evidenced by their elevated serum fatty acid and acylcarnitine levels, and relative hypoglycemia and hyperketonemia. In addition, although total serum carnitine levels were increased in both adult and weanling septic rats, tissue carnitine levels of weanling rats became significantly depleted during sepsis, unlike in adult rats. This study supports further investigation regarding the role of exogenous carnitine in newborn sepsis.

Effects of parenteral L-carnitine supplementation on fat metabolism and nutrition in premature neonates.

The effects of parenteral L-carnitine supplementation on fat metabolism, nutrient intake, and plasma and erythrocyte carnitine concentrations were studied in 43 very low birth weight infants. Infants were randomly assigned to control or carnitine-supplemented (50 mumol/kg per day) groups within two weight categories: group 1, 750 to 1000 gm, and group 2, 1001 to 1500 gm. Plasma total, free, and acyl carnitine levels, erythrocyte carnitine levels, serum beta-hydroxybutyrate and triglyceride levels, and total fat intake were monitored weekly until 50% of total caloric intake was met enterally. Neonates receiving carnitine had higher plasma carnitine levels than control groups (total carnitine: group 1, 75.2 +/- 22.9 vs 9.6 +/- 2.7 mmol/ml; group 2, 61.6 +/- 31.2 vs 13.0 +/- 9.2 nmol/ml). Levels of beta-OH-butyrate decreased from baseline in control neonates (group 1, 0.12 +/- 0.06 to 0.03 +/- 0.02 mmol/L; group 2, 0.11 +/- 0.03 to 0.05 +/- 0.02 mmol/L); they remained unchanged in supplemented groups. Thus ketogenesis appeared less impaired in infants receiving supplements. Supplemented group 2 tolerated more fat than control group 2; triglyceride levels remained acceptable in all groups. Carnitine group 2 had greater weight gain than control group 2 during the first 2 weeks of life. We conclude that very low birth weight infants requiring prolonged parenteral nutrition have carnitine deficiency with impaired ketogenesis. Parenteral administration of carnitine appears to alleviate this metabolic disturbance.