CARBOHYDRATE UTILIZATION BY CHICK EMBRYONIC HEART CULTURES

1960 ◽  
Vol 38 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Joseph F. Morgan ◽  
Helen J. Morton

Freshly explanted chick embryonic heart fragments were cultivated in completely synthetic media. Survival of such cultures in the complete medium, containing glucose, was established at approximately 35 to 40 days, while in the absence of carbohydrate the cultures died within 3 to 5 days. Survival was considered to be a more physiological measurement than rapid cell multiplication for normal tissues and was adopted as the criterion for all experiments reported. Fifty-two compounds were tested for their ability to replace glucose, as the sole carbohydrate, in this system. Of these, seven (mannose, fructose, galactose, β-glucose, maltose, glucose-1-phosphate, and glucose-6-phosphate) replaced glucose completely. Five others (sorbitol, alpha-methyl-D-glucoside, turanose, dextrin, and fructose-6-phosphate) were partially active. The remainder were negative. Comparison is made of the present results with those obtained by other workers using malignant cells in the presence of serum–enzymes. The present results suggest that the ability to replace glucose decreases progressively as compounds down the Embden–Meyerhof pathway are tested.

1960 ◽  
Vol 38 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Joseph F. Morgan ◽  
Helen J. Morton

Freshly explanted chick embryonic heart fragments were cultivated in completely synthetic media. Survival of such cultures in the complete medium, containing glucose, was established at approximately 35 to 40 days, while in the absence of carbohydrate the cultures died within 3 to 5 days. Survival was considered to be a more physiological measurement than rapid cell multiplication for normal tissues and was adopted as the criterion for all experiments reported. Fifty-two compounds were tested for their ability to replace glucose, as the sole carbohydrate, in this system. Of these, seven (mannose, fructose, galactose, β-glucose, maltose, glucose-1-phosphate, and glucose-6-phosphate) replaced glucose completely. Five others (sorbitol, alpha-methyl-D-glucoside, turanose, dextrin, and fructose-6-phosphate) were partially active. The remainder were negative. Comparison is made of the present results with those obtained by other workers using malignant cells in the presence of serum–enzymes. The present results suggest that the ability to replace glucose decreases progressively as compounds down the Embden–Meyerhof pathway are tested.


1979 ◽  
Vol 150 (4) ◽  
pp. 878-887 ◽  
Author(s):  
A L Reddy ◽  
P J Fialkow

The cellular origin of tumors induced by the chemical carcinogen 3-methylcholanthrene (MCA) was studied in mice with X-chromosome inactivation mosaicism. Because only one of the two X-chromosomes is active in XX somatic cells, a female heterozygous at the X-linked phosphoglycerate kinase (PGK-1) locus for the usual Pgk-1b gene and the variant Pgk-1a has two populations of cells, in the cells of one population, Pgk-1b is active and B-type enzyme is synthesized, whereas in cells of the other population, A-type enzyme is produced. Both enzyme types are found in normal tissues from these mosaic mice. A tumor developing from a single cell exhibits only one of the two PGK enzyme types, whereas a tumor with a multicellular origin expresses both enzymes (i.e., it has a double-enzyme phenotype). Five fibrosarcomas developing at the site of injection of 0.2 or 2.0 mg of MCA were analyzed. 36 of 38 fragments from the five tumors had double-enzyme PGK phenotypes. One piece from each of two tumors showed a single-enzyme phenotype. Histological, cell culture, and cloning studies indicate that the double-enzyme phenotypes reflect the presence of both types of malignant cells and not admixture of normal with neoplastic elements in the specimens tested for PGK. The results suggest strongly that these fibrosarcomas have a multicellular origin.


1957 ◽  
Vol 35 (10) ◽  
pp. 785-794 ◽  
Author(s):  
Joseph F. Morgan ◽  
Helen J. Morton

Previous studies on the sulphur amino acid requirement of freshly-explanted chick embryonic heart tissues cultivated in vitro in completely synthetic media have been extended. The essential requirement for L-cystine has been found to be replaceable by L- but not by D-cysteine. In the presence of L-cysteine, the supplementary methionine requirement was found to be satisfied equally by the L- or D-isomer. Of eight derivatives and metabolites of cysteine studied, only cysteamine showed any significant ability to replace cysteine or cystine. The activity of cysteamine was exhibited only in the presence of methionine. High levels of cysteamine were found to be strongly toxic and the toxicity could be reversed specifically by L-cysteine. Significantly less reversal of the cysteamine toxicity was effected by L-cystine, while other sulphydryl and disulphide compounds were ineffective. Cystamine was also found to be toxic to the tissue cultures and its toxicity could be reversed completely by L-cysteine and incompletely by L-cystine.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii305-iii305
Author(s):  
Diane Puccetti ◽  
Mario Otto ◽  
Daniel Morgenstern ◽  
Kenneth DeSantes ◽  
Steven Cho ◽  
...  

Abstract BACKGROUND CLR 131 is a novel targeted radiotherapeutic that exploits the selective uptake and retention of phospholipid ethers by malignant cells. CLR 131 selectively delivers radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. OBJECTIVE CLR 131 is being examined in a Phase 1 trial, CLOVER-2 (NCT03478462), to determine the safety, tolerability, and initial efficacy of CLR 131 in children and adolescents with relapsed/refractory malignancies. METHODS Eligibility criteria include children with relapsed or refractory solid tumors or malignant brain tumors for which there are no standard treatment options with curative potential. Subjects must be between ages 2 and 21 with no limit to the number of prior therapies. CLR 131 is administered as a single infusion in escalating doses beginning at 15 mCi/m2. Adverse events (AEs) are graded by NCI-CTCAE v5. RESULTS As of 10Jan2020, four subjects with brain tumors have received CLR 131; one at 15 mCi/m2 and three at 30 mCi/m2. Diagnoses included DIPG (2), glioblastoma (1), and medulloblastoma (1). Median age is 13 years (range 10–15) and patients received a median of two prior therapies (range 1 to 8). There were no treatment emergent AEs at the 15 mCi/m2 dose level attributed to CLR 131 by the investigator. Assessment of the 30 mCi/m2 dose level is ongoing. CONCLUSIONS CLR 131 is a unique, first in class targeted radiotherapeutic for pediatric malignancies. Preliminary data shows an acceptable and expected safety profile in this patient population. Dose escalation to determine the highest tolerated dose is ongoing.


Nature ◽  
1959 ◽  
Vol 183 (4669) ◽  
pp. 1201-1202 ◽  
Author(s):  
ARTHUR E. PASIEKA ◽  
JOSEPH F. MORGAN

1961 ◽  
Vol 14 (3) ◽  
pp. 349 ◽  
Author(s):  
FJ Bergersen

A chemically defined medium for the growth of Rhizobium is described in which populations of up to 5 x 109 cells/ml were obtained. For the six strains of bacteria studied the complete medium supported exponential growth for two to five generations. The concentrations of biotin giving best growth varied ith strain between 125 and 250 f'g/l when the nitrogen source was sodium glutamate. NHt, NOs, and other amino acids, singly or in combination, did not upport as good growth as did sodium glutamate.


1950 ◽  
Vol 34 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Wayne Hull ◽  
Paul L. Kirk

The effect of horse serum alone, and of embryo extract alone, was compared with that of "complete medium" on the content and synthesis of ribo- and desoxyribonucleic acids and uptake of tracer P32 by chick heart cultures in vitro. The factors mentioned are influenced by embryo extract in a manner similar to the effect in complete medium. Horse serum produced little synthesis of nucleic acids or uptake of tracer, giving only slightly more effect than Tyrode's solution alone. Cutting the tissue into smaller pieces caused considerably greater synthetic effects, and retarded necrosis of the implant.


1956 ◽  
Vol 34 (1) ◽  
pp. 619-636 ◽  
Author(s):  
Ernest Kovacs

Investigation of enzyme systems in normal tissues is the main subject of this communication. The activity of phosphatases, nucleotidases, and nucleases was explored in "brei" prepared with water, physiological salt mixtures, and synthetic media used for tissue cultivation, to compare the influence of these diluents. The depression of acid phosphatase by medium 597, noted previously in cells growing in vitro, was confirmed in fresh tissue and definitely proved on purified enzyme. Alkaline phosphatase was activated by the same synthetic medium. Differences in kinetics were observed when the effect of medium 597 was examined on 5-nucleotidase concentrate of Russel's viper venom and on pentanucleotidase of fresh kidney. Crystalline RNA-se was inhibited, in a manner similar to the nucleases of kidney extracts. Both phosphomonoesterases were enhanced by the less complex nutrient 697. The deterioration of DNA-se in medium 199 upon storage was striking. Significant observations were gathered on enzymes of concentrated and very diluted (1: 1600) tissue homogenates, on extracts, and on isolated enzymes of various grades of purity.


1957 ◽  
Vol 35 (1) ◽  
pp. 785-794 ◽  
Author(s):  
Joseph F. Morgan ◽  
Helen J. Morton

Previous studies on the sulphur amino acid requirement of freshly-explanted chick embryonic heart tissues cultivated in vitro in completely synthetic media have been extended. The essential requirement for L-cystine has been found to be replaceable by L- but not by D-cysteine. In the presence of L-cysteine, the supplementary methionine requirement was found to be satisfied equally by the L- or D-isomer. Of eight derivatives and metabolites of cysteine studied, only cysteamine showed any significant ability to replace cysteine or cystine. The activity of cysteamine was exhibited only in the presence of methionine. High levels of cysteamine were found to be strongly toxic and the toxicity could be reversed specifically by L-cysteine. Significantly less reversal of the cysteamine toxicity was effected by L-cystine, while other sulphydryl and disulphide compounds were ineffective. Cystamine was also found to be toxic to the tissue cultures and its toxicity could be reversed completely by L-cysteine and incompletely by L-cystine.


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