Glossary of abbreviations and definitions of nutritional terms.
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Biomedical subjects
Publications and source records attributed to M Friedman.
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Hair samples from seven sick Ghanaian children were analyzed for amino acids. Cystine was determined by a procedure of Friedman using tributylphosphine and 2-vinylpyridine to change residues of cystine (and cysteine, if present) to S-beta-(2-pyridylethyl)-L-cysteine (2-PEC). This acid-stable derivative is released by normal acid hydrolysis and is eluted as a well-resolved peak before lysine in conventional ion-exchange amino acid analysis. The average cystine content of six children suffering from kwashiorkor or marasmic kwashiorkor was found to be about 20% less than that of the one remaining child, whose protein nutrition was judged adequate. In view of conflicting evidence of the relation of hair cystine content and nutrition, we believe further definitive studies of this subject are urgent. No other substantial difference in amino acid composition was noted.
Of the several causes of gastric necrosis, the rarest is acute necrotizing gastritis which appears to be a variant of phlegmonous gastritis. In acute necrotizing gastritis all four major gastric vessels are patent, but gastric gangrene occurs secondary to an over-whelming necrobiotic infection. The case presented herein is of unusual interest because it appears to be only the third reported case of acute necrotizing gastritis with overt gangrene of the stomach. Review of the literature on suppurative gastritis emphasizes the rarity and high morbidity of acute necrotizing gastritis; the patient reported on in this study, however, survived after subtotal gastrectomy and antibiotic therapy. It is our opinion that debridement by gastrectomy must be performed in those patients with transmural, diffusely infected, nonviable gastric tissue.
Connective tissue composition of aortas from several non-human primate species has been studied in an effort to relate collagen, elastin, ang glycosaminoglycan (GAG) content to species susceptibility to atherosclerosis. Among the species studied the baboon contained the highest content of GAG in the aorta. While the distribution of individual GAG varied from species to species, heparan sulfate (HS) was the highest GAG in aortas from most of the species. The ratio of HS to chondroitin sulfates (CS) plus dermatan sulfate (DS) was lowest in the baboon, a species relatively less susceptible to atherosclerosis, and highest in the squirrel monkey, a very susceptible primate. If a relationship exists between HS to CS + DS ratio in the aorta and atherosclerosis, the primates can be arranged in the following decreasing order of susceptibility: squirrel, chimpanzee, stump-tailed, rhesus, African green, patas, baboon. In studies of other connective tissue components, the proportion of total collagen to elastin was found lowest in the baboon. Such observations emphasize the importance of connective tissue in the pathogenesis of atherosclerosis.
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Three patients who received simultaneous radiation and chemotherapy are described. Increased tumor response and enhanced radiation reaction were observed. Simultaneous drug and radiation therapy may prove to be the treatment of choice for particular malignant tumors. More data concerning the magnitude of the toxic effects when 2 modalities are used in conjunction is needed. Dose adjustments will be required for each modality to allow for optimal damage to the tumor with minimal and acceptable adverse reaction in the normal tissue.
The molecular structure of wool is discussed in relation to chemical reactivity and the role of disulfide crosslinks. Ideal characteristics of an effective medium (e.g. dimethylformamide) for modifying wool include the ability to penetrate and swell wool without interfering with reagents used. The extent of reaction of wool or reduced wool is compared for mono-and bifunctional activated vinyl compounds, isocyanates, acid chlorides, acid anhydrides, sulfonyl chlorides, and alkyl halides. The degree of crosslinking is assessed by solubility, supercontraction, and tensile tests. Optical and electron scanning microscopy can give evidence of external polymer deposition in contrast to internal chemical modification. Effects of crosslinking by bifunctional reagents are related to changes in mechanical, chemical, and biological (moth-resisting) properties of the modified wool.
Reductive alkylation of bovine serum albumin (BSA) and wool by a aromatic aldehydes and sodium cyanoborohydride has been investigated. The aldehydes used were chosen to allow convenient quantitative measurement of binding by ultraviolet spectroscopy. Alkylation of BSA occurred primarily at two highly reactive sites. Variation of time, PH, reactant concentration, and addition of urea had little effect on the extent of alkylation of BSA. However, more extensive alkylation was achieved in buffered aqueous dimethyl sulfoxide. The unusual reactivity of two epsilon-amino groups on the BSA molecule is attributed to closely placed lysine residues in the primary sequence rather than to favorable placement of unrelated, distant reactive centers. Similarly, only a few of the potentially available epsilon-amino groups of wool were observed to react.
The mass spectra of a series of cysteine derivatives of structure X-CH2CH2SCH2CH(NH2)COOH were examined to assess the influence of the electron-withdrawing functional group X on the mass spectral fragmentation patterns. Measurable molecular ions were present in most of the spectra although in some cases such peaks had relative abundances below a few per cent. More useful information on the nature of the substituent could be obtained from the M - 74 peak corresponding to cleavage C2H4O2N at the sulfur atom. The results show that mass spectroscopy is valuable for identifying the S-alkyl side chain in S-alkyl cysteine derivatives, a process frequently required in studies on chemical modification of sulfhydryl groups andin determining disulfide bonds in proteins. The observed fragmentation patterns are discussed in terms of localization of positive charges of ionic species on either sulful, nitrogen, or heterocyclic rings and in terms of substituent effects on available decomposition pathways.
Studies were carried out on the effect of decoupling, deuterium labeling, concentration, temperature, and solvent media on the NMR parameters of the vinyl phosphonate adduct of phenylalanine, C6H5CH2CH(COO-)NH2+CH2CH2PO(OCH2CH2C1)2. The results permit assignments of chemical shifts and coupling constants to the various protons of this molecule which contains unique structural features. The NH2+-CH2-protons are deshielded by more than 1 ppm than the CH2-PO-protons. The -OCH2-protons are nonequivalent exhibiting a fine split. Possible sources of the fine split include NH...O=P hydrogen bonding. The deuterium-labeling method should be applicable for synthesizing deuterium-and tritium-labeled crosslinked amino acids such as lysinoalanine and lanthionine and demonstrating analgous dehydroalanine-alpha-amino group-crosslinking.
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Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins.
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Chemical treatment of proteins in feeds can, by crosslinking protein chains or other chemical effects, decrease their solubility and microbial degradation in the rumen. A need exists to modify proteins systematically under well-defined conditions with inexpensive reagents and to evaluate the treated products nutritionally for possible beneficial effects on wool growth and quality as well as production of meat and milk. As a first step toward this goal we evaluated many derivatives of casein treated at pH 9-10 with various acylating and alkylating agents. Initial tests indicate that all treatments decreased protein digestion by rumen microorganisms. Potentially crosslinking reagents are usually more effective than similar ones that cannot crosslink. A few treatments gave ruminal protection that approached or exceeded that obtained with formaldehyde. This result shows that systematic evaluation of ruminal in vitro digestibility of protein derivatives may disclose new products deserving tests of post-ruminal digestibility and practical nutritive value.
The pharmacological and therapeutic action of penicillamine are very largely explained by its ability to chelate metal ions and take part in oxidation-reduction reactions, sulfhydryl-disulfide interchange, and nucleophilic addition. Effects of penicillamine on particular enzymes are explained by its chemical properties. Possible interactions with amino acids, tissue proteins, food constituents, and intermediates in the metabolism and biosynthesis of sulfur containing amino acids are discussed.
Alkali treatment of food proteins converts some amino acid residues to the unnatural amino acid lysinoalanine which has been found to cause kidney damage when fed to rats. Formation of lysinoalanine was essentially prevented when isolates of soy protein and casein were exposed to alkali in the presence of thio-alamino acids such as cysteine. The results suggest that added thiols minimize the formation of potentially toxic lysinoalanine.