[The problem of remelting cobalt-chromium alloys (Part 2)].
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Biomedical subjects
Publications and source records attributed to K Langer.
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A female patient with acrodermatitis chronica atrophicans and widespread sclerodermiform skin lesions with a high IgG antibody titer against Borrelia burgdorferi is presented. The rapid improvement after high-dose penicillin G therapy and the course of the Borrelia antibody titer suggest a persistence of the causative organism.
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Several high-performance liquid chromatographic (HPLC) methods are described for separation of peptide stereoisomers which are not well resolved by traditional reversed-phase chromatography. These chiral HPLC methods include investigations with a beta-cyclodextrin column, a Pirkle D-Phenyl Glycine column and a Chiral-Pak WH column. A method based on derivatization of dipeptides with a chiral reagent, N-acetyl-L-cysteine and o-phthalaldehyde, is also discussed. A series of linear and cyclic dipeptides and modified amino acids were chromatographed on the four systems. Resolution varied for the four different systems depending on the types of compounds that were chromatographed.
Pathways of glutamine metabolism in resting and proliferating rat thymocytes were evaluated by in vitro incubations of freshly prepared or 60-h cultured cells for 1-2 h with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76 and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for 25 and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in both cells is transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37 and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations.
Peripheral blood mononuclear cells (PBMC) from 40 patients with gastrointestinal carcinoma (GIC), 13 patients with primary carcinoma in other localizations(non-GIC), and from 57 apparently healthy donors were isolated by Ficoll-Paque gradient centrifugation. The separated cells were stained with several monoclonal antibodies and subjected to analysis on a fluorescence-activated cell sorter. A decreased percentage of PBMC expressing T cell antigens was noted amongst GIC patients, and was mainly due to a reduction of the Leu 2a subset, thus, leading to an increase in the Leu 3a/Leu 2a ratio from 1.4 to 2.1 Non-GIC patients had decreased numbers of both T helper and suppressor cells. Amongst PBMC from GIC and non-GIC patients a statistically increased percentage of cells expressed LeuM 2 (P less than 0.001), LeuM 3 (P less than 0.001), OKM 1 (P less than 0.005), VEP 9 (P less than 0.001), and HLA-DR (P less than 0.001) antigens compared to healthy controls. The percentage of cells bearing these monocyte/macrophage antigens correlated well with the number of cells having monocyte morphology, stained for non-specific esterase, phagocytosed latex particles, and expressed Fc IgG receptor. Our results demonstrate clearly that tumor-bearing patients have an increased relative number of monocytes. The data suggest that cells of the macrophage lineage may be involved in defense mechanisms and changes of the immune system evoked by various tumors.
Obesity was associated with a significant increase in postabsorptive plasma concentrations of the branched-chain keto acids in men but not in women matched for body-mass index and age. Plasma glucose and serum insulin were significantly higher in obese subjects than in nonobese control subjects. Obese women had more adipose tissue than did obese men from the sum of triceps and subscapular skinfold thickness. It is suggested that augmentation in plasma branched-chain keto acids in obesity may reflect insulin resistance and that the apparent differences observed between obese women and men may be due to differences in body composition.
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Ten healthy human subjects received parenteral nutrition consisting of 80 g of a dipeptide-amino acid mixture and 900 carbohydrate calories infused over a period of 12 h, and then fasted for another period of 12 h. The dipeptides included in the mixture were: glycyl-L-glutamine, glycyl-L-tyrosine, glycyl-L-leucine, glycyl-L-isoleucine, and glycyl-L-valine. Parenteral nutrition with the dipeptide-amino acid mixture was without any adverse reaction in any of the subjects. The urinary excretion of the 5 dipeptides during parenteral nutrition ranged between 1 and 2% of the amount infused. Plasma concentrations of dipeptides during parenteral nutrition, which ranged from 8-96 microM reflected their plasma half-lives. Glycyl-L-glutamine had the longest half-life, glycyl-L-leucine and glycyl-L-tyrosine the shortest half-lives. During parenteral nutrition there were increases in plasma amino acid concentrations including those of glutamine and tyrosine. Discontinuation of parenteral nutrition resulted in the disappearance of dipeptides from plasma, and the dissipation of increased plasma amino acid concentrations. In conclusion, the present results show efficient utilization of glycyl-dipeptides as substrates for parenteral nutrition in man. The results further show that the structure of amino acids in the C-terminal position has a significant influence on the metabolism of dipeptides.
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Utilization of methionine and N-acetyl-L-cysteine as a source of cysteine was tested in growing rats receiving total parenteral nutrition for four weeks. The three solutions tested were isonitrogenous and isocaloric. One of the solutions contained an adequate amount of L-methionine, in the other two, two thirds of the L-methionine was substituted by a corresponding amount of either glycine or N-acetyl-L-cysteine. Weight gain and N-balance were similar under the infusion with either the adequate amount of L-methionine or the N-acetyl-L-cysteine substituted. The solution in which two thirds of the L-methionine was replaced by glycine yielded only half of the weight gain and correspondingly reduced values for N-balance. The daily urinary excretion rate for N-acetyl-L-cysteine was 4.6% of the infused amount. Urinary excretion rates of the other amino acids and the plasma amino acid pattern was affected differently by the three solutions. The results indicate that cysteine is more rapidly available from N-acetyl-L-cysteine than from L-methionine when administered intravenously.
We investigated parameters of nutrition, metabolism, and organ function after 4 wk of total parenteral nutrition (TPN) in baboons receiving either dipeptides or amino acids as the nitrogen source. The two groups showed no significant difference with respect to gain in body weight, nitrogen balance, plasma and muscle concentrations of amino acids, plasma concentrations of proteins, and leucine incorporation into muscle protein. All dipeptides were efficiently utilized as evidenced by trace concentrations of dipeptides in plasma and urine; they produced no deleterious effect on the function of liver, kidney, or immune system. Development of infection in several baboons increased urinary excretion of urea nitrogen but had no effect on urinary excretion of dipeptides and amino acids with the single exception of taurine, which was greatly increased. In conclusion, the data show long-term efficacy and safety of the dipeptide mixture as the sole nitrogen source for TPN.
Using a subhuman primate (baboon) we have investigated the utility of a 20% mixture of amino acids and dipeptides as the nitrogen source for total parental nutrition. The mixture, besides containing all 8 essential amino acids and a number of non-essential amino acids (glutamate, aspartate, arginine, histidine, serine, ornithine and alanine), contained 6 dipeptides (Gly-Ile, Gly-Leu, Gly-Val, Gly-Tyr, Gly-Gln, and Ala-Gln) and acetyl-cysteine. A week of total parenteral nutrition was preceded by one week of oral feeding. The caloric intake and composition during the two periods was identical except for the nitrogen source, which was intact protein during the oral period, and the mixture of amino acids and dipeptides during the parenteral period. There was no significant difference between gain in body weight or nitrogen balance during the two periods. There were selective increases in plasma and muscle concentrations of amino acids during the parenteral period, which appeared to reflect the amino acid enrichment of the nitrogen source. The efficient utilization of dipeptides was evidenced by their small concentrations in plasma and urine. The urinary excretion of dipeptides was about 1% of the amount infused. This efficiency of dipeptide utilization persisted even when the infusion rate of the amino acid and dipeptide mixture was increased by 7-fold. There was no alteration in liver, kidney, and immune function during the parenteral period. The data indicate the efficacy and safety of the mixture of amino acids and dipeptides as the nitrogen source for parenteral nutrition.
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Utilization of N-acetyl-L-tyrosine and glycyl-L-tyrosine as a source of tyrosine in infusion solutions was tested in rats receiving total parenteral nutrition for 4 wk. The four solutions tested were isonitrogenous and isocaloric. One of the solutions contained an adequate amount of L-phenylalanine; in the other three, two-thirds of the phenylalanine was replaced by a corresponding amount of either glycine, glycyl-L-tyrosine or N-acetyl-L-tyrosine. No differences in weight gain or N-balance could be detected as a result of administering either the solution with glycyl-L-tyrosine or with N-acetyl-L-tyrosine in place of the solution containing an adequate phenylalanine content. The solution in which two-thirds of the L-phenylalanine was replaced by glycine yielded only half of the weight gain and correspondingly reduced values for N-balance. Daily urinary excretion rates for N-acetyl-L-tyrosine and glycyl-L-tyrosine were 11% and 0.5%, respectively, of the infused amount. Plasma amino acid pattern was affected differently by the four solutions. The results indicate that both N-acetyl-L-tyrosine and glycyl-L-tyrosine are efficiently utilized by the rat during total parenteral nutrition.
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For determination of a drug in biological fluids, accuracy and sensitivity of detection of the adopted method are decisive parameters, but practical aspects such as time and necessary instrumentation are equally important. In the case of N-acetyl-L-cysteine, sample pretreatment can be kept at a minimum if sufficiently selective modes of derivatization, chromatography and detection are employed. Its concentration in serum is between 1 and 20 mumol/l; for quantitative analysis capillary gas chromatography and mass fragmentographic detection are employed. For urine with its ten-fold higher concentration the preferred method is reversed-phase high-performance liquid chromatography after thiol-selective derivatization.