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Biomedical subjects

R H Matthews

Publications and source records attributed to R H Matthews.

At least 37 records · Page 2Linked to original sources

Interaction of 2-aminobicyclo[3.2.1]octane-2-carboxylic acid with the amino acid transport systems of the sarcoma 37 murine ascites tumor cell.

The relatively broad and overlapping specificities of amino acid transport systems have made the synthesis of analogues specific to single transport systems desirable. The analogue in general use as a specific substrate for transport system L has been 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH). The affinity of BCH for the binding site of system L has been shown to be less than that of the natural substrate, leucine. Earlier studies from this laboratory suggested that higher homologues in a series could have greater affinity for system L. A higher homologue of BCH, 2-aminobicyclo[3.2.1]octane-2-carboxylic acid (ABOCA), has been synthesized and studied as a substrate and competitor for amino acid transport systems of the sarcoma 37 (S37) ascites cell. ABOCA inhibited the transport system dominant in the low concentration region for histidine uptake (system L) but had no effect on the uptake of labeled N-methyl-alpha-aminoisobutyric acid (MeAIB). MeAIB had no effect on labeled ABOCA uptake in S37 cells. ABOCA inhibited the uptakes of labeled leucine and labeled BCH competitively. Leucine, histidine, and BCH inhibited the uptake of labeled ABOCA competitively. Typical L system substrates demonstrated exchange effects with labeled ABOCA. The b isomer of ABOCA demonstrated slightly greater affinity for system L than did the a isomer. We conclude that ABOCA is an analogue restricted to interaction with amino acid transport system L, that it has greater affinity for system L than does BCH, and that its selection for system l is determined principally by an apolar interaction with steric considerations secondary.

Amino Acids↗

Biochemical subgrouping of benign breast disease to define premalignant potential.

To determine which subgroups of benign breast disease are likely to progress to malignant degeneration, a biochemical analysis of 3'5' cyclic adenosine monophosphate (cAMP) was run on several samples of breast tissue. cAMP is elevated in a progressive fashion from normal breast tissue to fibrosis, cystic mastitis, ductular hyperplasias, and finally to carcinoma. Correlation of cAMP levels in breast lesions with histopathologic grading of increasing epithelial proliferation confirmed the concept that there are subgroups within those lesions that have greater malignant potential. Benign breast lesions with significantly higher cAMP levels, although still lower than those of cancer, must be considered at higher risk for eventual malignant change.

Adenylyl Cyclases↗

Inhibition of S37 ascites cell amino acid transport systems by alpha-chloromethylketone analogs.

Alanine chloromethylketone and leucine chloromethylketone were synthesized and their effects on amino acid transport in sarcoma 37 mirone ascites tumor (S37) cells were studied. Alanine chloromethylketone preincubation weakly inhibited system A. Leucine chloromethylketone preincubation strongly inhibited both amino acid transport systems L and A. Leucine chloromethylketone was also a competitive inhibitor of leucine transport. Labeled leucine chloromethylketone was concentrated by S37 cells. Leucine chloromethylketone preincubation inhibition was concentration dependent and partial protection of transport was afforded by leucine. Steady-state retention of amino acids was decreased more than the initial velocity of transport by leucine chloromethylketone preincubation. Glutathione was also depleted. Labeled leucine chloromethylketone was incorporated in a plasma membrane protein fraction comigrating on a DEAE-cellulose column (DE52) with gamma-glutamyltranspeptidase activity. There was a modest increase in vital staining after treatment of S37 cells with leucine chloromethylketone, and glucose uptake was also inhibited. Whilst several effects occur during treatment of S37 cells with leucine chloromethylketone, it is suggested than one prominent effect is alkylation of amino acid transport system components.

Alanine↗

Methionine transport in S37 cells. Substrate-dependent function of amino acid transport system A in exchange processes.

Methionine had been observed to interact with two principal transport systems for amino acids in mammalian cells, the A and L systems. The present study of methionine transport and of exchange processes through system A arose in the course of a study to define the specificity of a transinhibition effect caused by cysteine. Methionine uptake through two transport systems in the S37 cell was confirmed by the occurrence of a biphasic double-reciprocal plot for labeled methionine uptake. Preloading cells with methionine stimulated labeled histidine uptake through systems A and L. Efflux of labeled methionine from cells was stimulated by histidine in a biphasic manner, so that bothe systems A and L can be used for exchange when methionine is the intracellular amino acid. Aminocycloheptanecarboxylic acid elicited exchange efflux of labeled methionine only through system L. ALPHA-Aminoisobutyric acid and N-methyl-alpha-aminoisobutyric acid both stimulated efflux of labeled N-methyl-alpha-aminoisobutyric acid from S37 cells. These findings are interpreted a showing that transport system A is capable of functioning as an exchange system depending upon the identity of intracellular and extracellular substrates available.

Amino Acids↗

Diabetes and cancer: a postulated relationship.

Diabetes leads to periodic fluctuations in levels of nutrients and cyclic nucleotides in plasma and various tissues. Variations in cyclic nucleotide levels, periods of nutrient elevation and surges of insulin combine to stimulate growth. Growth stimulation may be associated with the promotional phase of carcinogenesis. Diabetes should therefore predispose the individual to carcinogenesis and limited epidemiological data available suggest that it does.

Amino Acids↗

Caffeine, cyclic nucleotides, and breast disease.

Methylxanthine consumption is associated with the development of fibrocystic disease of the breast. Methylxanthine abstention is associated with resolution of signs and symptoms of fibrocystic disease. Abstinence from methylxanthine consumption decreased breast biopsies and the need for major breast surgery because of benign disease. Methylxanthine consumption is associated with elevated cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) values in fibrocystic dsiease over those obtained in normal breast tissue.

Adenosine Monophosphate↗

Synthetic sulfur-containing amino acids. Inhibition of transport systems in S37 ascites tumor cells.

The preparation of a series of synthetic sulfur-containing amino acids is described. These compounds included heterocyclic analogues of L-cysteine, DL-norcysteine, and DL-homocysteine. The amino acids were assessed for their ability to inhibit the neutral amino acid transport systems of the Sarcoma 37 ascites tumor cell and their inhibitions were compared with those of L-methionine and L-ethionine. Transport studies indicated that the amino acids synthesized were capable of inhibiting the uptake of [3H]-L-histidine in the S37 cell.

Amino Acids↗

Nutrient content of selected baby foods.

Nutrient content often varies somewhat among brands of baby foods today. Dinners, such as vegetables and meat, are higher today in moisture content than when Agriculture Handbook 8 was published in 1963. Modern processing techniques may account for this difference. To combat nutritional anemia, dry cereals, often the baby's first food other than milk or formula, are excellent sources of good-quality protein and iron, as well as of copper. Asorbic acid is often added to fruits and fruit juices to improve and standardize the product. In recent years, sodium in baby foods has been reduced, due to limited use of salt and monosodium glutamate. Trends indicate less sugar will be added to fruits and juices in the future. Variation in content of selected nutrients can be attributed to the proportion of ingredients in the mixture or the variety of vegetable or fruit selected by the baby food processor.

Anemia↗

Effects of cysteine upon tumor cells.

Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.

Amino Acids↗

In vivo synchronization of murine sarcoma 37 ascites tumor cells by use of hydroxyurea.

Synchrony of DNA synthesis in mouse sarcoma 37 ascites cells was achieved in vivo by injection of 0.75 mg hydroxyurea per gram weight of mouse. DNA synthesis was gauged by comparing 3H-labeled thymidine incorporation, under defined conditions, to total DNA measured colorimetrically. DNA synthesis in the sarcoma 37 cells fell to negligible levels 4 hours after injection and remained at or below levels observed in randomly dividing cells up to 18 hours after injection. A sharp increase in DNA synthesis occurred at 20 hours, followed by a decline again at 22 hours after hydroxyurea injection. DNA synthesis in the intestine remained below control values at 20 hours.

Animals↗

Estimation of surface area and counterion binding characteristics in fatty amine monolayers from desorption kinetics.

The surface area per molecule of an un-ionized fatty amine is very similar to the surface area per molecule of an un-ionized fatty acid. Surface area increases with ionization in both fatty amine and fatty acid films. However, fatty amino cations have much smaller surface areas than the corresponding fatty acid anions. Thus counterion binding is stronger with fatty amine cations than with fatty acid anions. Surface area data show that counterion binding affinities for fatty amine cations decrease in the strong field sequence Cl- greater than Br- greater than I- greater than SCN-. Furthermore, surface areas in the presence of the most strongly bound counterions, Cl- and Br-, increase significantly with an increase in subphase ionic strength. These data are consistent with the formation of strong ion-pair bonds and their disruption with an increase in ionic strength. Fatty amine cations desorb as micelles with much lower relative diffusion coefficients than the corresponding fatty acid anions. Furthermore, relative diffusion coefficients for fatty amine cations are strongly dependent on the specific cation. These data show that fatty amine cations form larger micelles when they desorb in the presence of strongly bound counterions. Anions enhance the solubility of a fatty acid anion in the sequence Cl- less than I- less than SCN-, which is characteristic of chaotropic anions that disrupt water structure.

Amines↗

Guidelines for determining and reporting food yields.

The author discusses problems in compiling and evaluating data and recommends a standard protocol for determing yield of food. The recent extensive revision of Agriculture Handbook No. 102, Food Yields Summarized by Different Stages of Preparation, points up the urgent need for guidelines and a standard protocol.

Animals↗