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Biomedical subjects

H W Wallace

Publications and source records attributed to H W Wallace.

At least 19 recordsLinked to original sources

Effect of retained components of excised tumor upon coexisting tumor.

Effects of locally treated and retained tumor tissue on the growth of a tumor at another site were investigated using Lewis rats bearing syngeneic fibrosarcoma. When an established tumor had completely regressed upon repeated intratumoral injections of L-phenylalanine mustard (PhM), the growth of secondarily transplanted tumor cells was inhibited. However, early excision of the PhM-injected tumor prevented the development of this effect. To study this effect directly, we excised one of the two established tumors in each thigh, and reinoculated into the excision wound either freeze-lysed 1 X 10(8) tumor cells (TC) or lysate chemically modified with PhM (PTC). We found that TC inoculation into the excision wound in 7 rats inhibited the growth of the remaining tumor and extended survival time (mean +/- SE, 27 +/- 1 days). With inoculation of PTC into the excision wound, the remaining tumor regressed and survival was significantly prolonged (32 +/- 2 days). In contrast, 7 untreated rats, each bearing two tumors, had a mean survival time of 22 +/- 0.1 days. Excision of one tumor (6 rats) did not affect the growth of the remaining tumor or survival time (23 +/- 1 days). We employed PhM to modify the immunogenicity of TC. However, if PhM dissociates from PTC, its cytotoxic effect may directly inhibit growth of the distant tumor. To examine this possibility, we divided 30 rats who had excision of one tumor, into three groups of 10 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Preservation of donor heart function and high-energy stores by continuous perfusion with synthetic plasma at 22 degrees C.

We evaluated high-energy phosphate (HEP) levels and the ability to perform work in rat hearts preserved by standard techniques (0.9% NaCl arrest and storage at 4 degrees C) and by continuous coronary perfusion at 22 degrees C, pH 7.25, and 55 mm Hg for 4 or 8 hr with Krebs-Henseleit buffer (KHB), modified Morgan's solution (MCS), or a medium developed in our lab (physiologically complete medium or PCM). Cardiac work was evaluated in the rewarmed hearts with use of a working heart preparation at left atrial pressures of 10, 15, and 20 cm H2O, and by measurement of aortic flow, coronary flow, heart rate, and peak systolic pressure. HEP levels in the hearts continuously perfused were significantly higher (p less than .05) than those in the hearts stored at 4 degrees C. The functional recovery of hearts preserved by storage in cold saline for 4 or 8 hr was significantly less (p less than .01) than the recovered function of hearts preserved for comparable periods by perfusion at 22 degrees C with either MCS or PCM. The results indicate that continuous perfusion at 22 degrees C with a more physiologic medium is superior to hypothermic arrest and storage at 4 degrees C for the preservation of donor heart function and HEP levels.

Animals

Artificial red cells with crosslinked hemoglobin membranes.

Artificial cells containing concentrated hemoglobin (Hb) solution were prepared by interfacial polymerization of Hb with glutaraldehyde (GA) in liquid membrane capsules (LMC). A solution containing 30% of Hb was emulsified in mineral oil as red cell-size microdroplets, and this emulsion was dispersed in an aqueous phase containing glutaraldehyde to form LMC. The LMC were semipermeable templates that held the microdroplets of Hb in suspension while GA diffused through the oil to the microdroplet surfaces. The GA crosslinked Hb at the surface of each microdroplet to form an artificial red-cell membrane encapsulating Hb solution. A water-soluble surfactant was used to eject the cells from the LMC and suspend them in saline. Several surfactants were evaluated. Cell size was controlled by agitation speed during preparation of the original emulsion. Cells of 2.52 = +/- 1.69 micron were prepared. The encapsulated Hb retained capacity to bind and release O2. The cells had a P50 of 8.9 torr (1200 Pa) and a capacity of 0.55 cc O2/g of total Hb, indicating that the crosslinked portion of the Hb did not contribute to O2 transport.

Blood Substitutes

Effect of nutritional status and 5-fluorouracil on protein synthesis in parenterally alimented LEW/Mai rats.

LEW/Mal rats bearing transplantable adenocarcinomas were maintained parenterally for 4 days on 1) a regimen adequate in amino acids and glucose and 2) severely hypocaloric glucose. Rats from both groups were given 17.5 mg 5-fluorouracil (FUra)/kg/day as a continuous infusion for 3 days. Cumulative nitrogen balance, fractional tissue protein synthesis rates, and liver and muscle distribution of FUra and its metabolites were determined. Results were compared to those found with a series of control rats that were not treated with FUra. No changes attributable to FUra were found in the starved rats (1.25 g glucose/day). In the fed rats (15 g glucose plus 2.5 g amino acids/day), FUra decreased the liver and diaphragm fractional protein synthesis rates and the nitrogen retention.

Adenocarcinoma

Relative rates of tumor, normal gut, liver, and fibrinogen protein synthesis in man.

Fractional protein synthesis rates of tumor, normal intestinal tissue, liver, and fibrinogen were measured in a series of patients with gastrointestinal malignancies. Protein synthesis rates were measured by the continuous infusion of 95+% [15N]glycine. Twelve to eighteen hours prior to the clinically indicated surgical excision of the tumor, 1-2 g of 95+% [15N]glycine was infused at a constant rate into each subject. During the surgical procedure, 0.05-2 g of tumor, normal intestinal tissue, liver, and 30 ml of venous blood were obtained. Protein synthesis rates were estimated from the ratio of 15N incorporated into tissue protein to the 15N enrichment of the tissue-free amino acid pool. The major findings were: i) the 15N enrichment of the tissue-free amino acids in malignant tissue was greater than and proportional to that in the corresponding normal tissue (P less than 0.02); ii) tumor protein synthesis rates were greater and proportional to the corresponding intestinal tissue rates (P less than 0.05); iii) the fibrinogen synthesis rate was greater than the liver protein synthesis rate (P less than 0.01), but there was no correlation between them.

Adult

Human platelet and fluorochemical interaction.

Since the fluorochemicals have become of interest for the development of artificial red blood cells, oxygenators, liquid breathing, and as a radiographic contrast medium, their interaction with biological substances is of importance. Fresh human platelets were placed in contact with four different fluorochemicals for a period of 50 min. The platelet function as measured by aggregation was determined before and after fluorochemical contact. Appropriate controls were also evaluated. No significant differences were found between the aggregation of platelets contacted with fluorochemicals and the aggregation of platelets from the same donor unexposed to fluorochemicals.

Biocompatible Materials

Changes in protein synthesis after trauma: importance of nutrition.

The effect of trauma (femur fracture) on protein synthesis in rats given four different parenterally administered nutrient formulations ("diets") was investigated. Diet I was a maintenance formulation. It contained sufficient amino acids and glucose to keep the rats in nitrogen balance but was inadequate to support growth. Diet II was amino acids only, diet III was severely hypocaloric glucose, and diet IV was diet I minus the amino acids. The rats received parenterally all nutrients for the duration of the 4-5 day study. Twenty-four hours posttrauma, the fractional synthesis rates of liver, lung, heart, kidney, and muscle were estimated by infusing [15N]glycine for 17.5-19 h. (T.P. Stein, J.C. Oram-Smith, M.J. Leskiw, H.W. Wallace, L.C. Long, and J.M. Leonard. The effects of protein and calorie restriction on protein synthesis in the rat. Am. J. Physiol. 230: 1321-1326, 1976.) Two trends were found: i) on the amino acid-containing diets (I and II), most protein synthesis rates were increased posttrauma. Lung was the exception: no change was found; ii) rats on the amino acid deficient diets (III and IV) showed a decrease in the fractional muscle and lung synthesis rates posttrauma. We concluded that in this rat trauma model the requirement is mostly for amino acid nitrogen posttrauma.

Amino Acids

Effect of nitrogen and calorie restriction on protein synthesis in the rat.

The effect of a deficiency of calories and/or nitrogen on protein metabolism in the rat was investigated. During the 5 days of the study, the rats received all nutrients except water via intravenous hyperalimentation. Four diets were used: I) 1.25 g amino acids, 12.5 g glucose/day; II) 1.25 g amino acids/day; III) 1.25 g glucose/day; and IV) 12.5 glucose/day. The rate of protein synthesis in heart, lung, muscle, kidney, and liver was estimated by a modification of the technique of Garlick et al. (The diurnal response of muscles and liver protein synthesis in vivo in meal-fed rats. Biochem. J. 136: 935-945, 1973) except that [15N]glycine was used as the tracer. Heart and lung protein synthesis was depressed by both caloric and nitrogen restriction. Muscle protein synthesis was only significantly affected by omission of calories from the diet. Kidney nitrogen content increased with the amino acid diets and decreased with the nitrogen-deficient diets. The major response of the liver to a dietary deficiency was to lose nitrogen via an increase in the rate of liver protein catabolism.

Animals

Equilibration of 15N-labeled amino compounds in man.

Following an overnight fast, either 15N-labeled glycine, or ammonium chloride, or L-aspartate was orally administered to human volunteers in equal hourly aliquots for 8-12 h. In a parallel series of experiments, [15N]glycine and [15N]ammonium chloride were given intravenously at a constant rate for 10-12 h. The amount of 15N given ranged between 2.7 and 27.3 mg/h. Five hundred milligrams of sodium benzoate were given hourly. Venous blood and urine samples were collected serially. The 15N enrichment of the plasma amino nitrogen, urinary ammonia, hippuric acid, and urea were determined. Irrespective of the 15N carrier used or the route of administration, the plasma amino nitrogen, urinary ammonia, and hippuric acid 15N enrichments approached a plateau within 6-10 h. We concluded that human [15N]glycine metabolism was not atypical of amino acids and that mixing, rather than nitrogen interchange reactions, determines the rate in attaining an approximate plateau.

Amino Acids