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Biomedical subjects

J Booyens

Publications and source records attributed to J Booyens.

At least 37 records · Page 2Linked to original sources

The effect of dietary supplementation with gamma-linolenic acid on the growth of induced tumours in rats.

In two identical experiments involving a total of 40 rats the effect of daily dietary gamma-linolenic acid (GLA) supplementation on induced tumour growth was investigated. It was found that GLA supplementation did not have an effect on tumour induction, tumour growth or survival time. The validity of the model used, infection of rats with human hepatoma cells, could be questioned.

Administration, Oral↗

Some effects of linoleic acid and gamma-linolenic acid on the proliferation of human hepatoma cells in culture.

In previous communications the growth-suppressive effect of gamma-linolenic acid (GLA) dissolved in sodium carbonate in the culture media of malignant cells has been reported. In this study we show that linoleic acid (LA), the fatty acid precursor of GLA, had no growth-suppressive effect on human hepatoma cells in culture while a similar concentration of GLA suppressed malignant cell growth in culture by 69% after 10 days. This growth-suppressive effect must therefore be seen as an effect of GLA and not as a 'soap' effect. It has also been shown that the growth rate of human hepatoma cells in culture to which GLA was added daily for 5 consecutive days remained suppressed after the withdrawal of GLA from the growth medium for a further 5-day period. The striking difference between GLA and LA as regards growth suppression of human hepatoma cells in culture appears to imply a metabolic block in the hepatoma cells, involving the enzyme delta-6-desaturase, in the conversion of LA to GLA and thence via dihomo-gamma-linolenic acid to the prostaglandins of the 1 series.

Antineoplastic Agents↗

The effect of gamma-linolenic acid on the growth of human osteogenic sarcoma and oesophageal carcinoma cells in culture.

A statistically highly significant growth-suppressive effect of the prostaglandin precursor gamma-linolenic acid (GLA) on MG63 human osteogenic sarcoma and oesophageal carcinoma cells in culture was found. In view of the results reported on the growth-suppressive effect of GLA on cancer cells in culture, on transplanted mammary tumours in rats and in primary liver cancer patients, it would appear that further investigation of the effects of this fatty acid on cancer cell growth both in vitro and in vivo is warranted.

Carcinoma↗

Some effects of the essential fatty acids linoleic acid and alpha-linolenic acid and of their metabolites gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and of prostaglandins A1 and E1 on the proliferation of human osteogenic sarcoma cells in culture.

Gamma-linolenic acid has been shown to suppress the rate of proliferation of a number of malignant cell lines in culture. To test the proposal that this was a specific prostaglandin 1- or 2-series effect, 379 batches of MG63 human osteogenic sarcoma cells were seeded in Greiner flasks and cultured in media supplemented with a range of unsaturated fatty acids and prostaglandins. The monounsaturated fatty acid oleic acid enhanced the rate of cancer cell proliferation. The polyunsaturated fatty acids linoleic acid, gamma-linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as prostaglandins E1 and A1 suppressed the rate of cell proliferation. Total suppression of colony forming and cell proliferation occurred at high levels of polyunsaturated fatty acid supplementation. In addition gamma-linolenic in the form of evening primrose seed oil and vitamin C has been given to 6 patients with histologically diagnosed primary liver cell cancer. Some clinical improvement and reduction in tumor size occurred in 3 cases. One patient has shown remarkable improvement in reduction of liver and tumor size on the CAT scan and reduction of the serum alkaline phosphatase from 2830 to 295 units and gamma-glutamyl transaminase from 274 to 82 units. Thus preliminary clinical results suggest that gamma-linolenic acid may be effective in the management of human cancer patients and further trials should be conducted. However, the cell culture results suggest that although the essential fatty acids suppress proliferation, eicosanoids of all 3 series may be involved. The proliferation suppressive effect of docosahexaenoic acid suggests that other aspects than only eicosanoid activity may also be important in the suppression of cancer cell proliferation.

Alprostadil↗

Cancer: a simple metabolic disease?

Recent studies on the effects of the essential fatty acid metabolic intermediate, gamma-linolenic acid, on the growth of cancer cells in culture and on induced mammary cancer tumours in rats, strongly suggest that the metabolic defect in the cancer cells studied is simply a metabolic block involving the enzyme delta-6-desaturase. The latter enzyme is responsible for the conversion of linoleic acid to gamma-linolenic acid. These observations would suggest that cancer in the cell lines studied could be a relatively simple metabolic disease.

8,11,14-Eicosatrienoic Acid↗

The effect of the prostaglandin derivative PGBx on calcium uptake and release by skeletal muscle sarcoplasmic reticulum.

The effects of the prostaglandin derivative PGBx on calcium release and uptake by skeletal muscle sarcoplasmic reticulum (SR) and on (Ca2+ + Mg2+)- adenosine triphosphatase (ATPase) activity were studied using skeletal muscle from rabbit hind legs. Both calcium uptake and Ca2+-ATPase activity were significantly inhibited by PGBx. Addition of PGBx to SR vesicles resulted in the release of calcium. It is proposed that this action of PGBx could be effected by the inhibition of ATPase and resulting passive release of calcium. The possibility also exists that PGBx could decrease the capacity of the SR vesicles for calcium in addition to any possible ionophoretic properties.

Adenosine Triphosphate↗

Some effects of gamma-linolenic acid on cultured human oesophageal carcinoma cells.

Cells of two continuous human oesophageal carcinoma lines were treated by the addition of gamma-linolenic acid (GLA) at concentrations of 10-60 micrograms/ml culture medium. After 7 days of exposure to GLA, pronounced morphological changes became evident and culminated in cell death. GLA-mediated effects were time- and dose-dependent and varied slightly with the degree of histological differentiation of the lines tested. These findings may have clinical implications.

Antineoplastic Agents↗

The reversibility of cancer: evidence that malignancy in human hepatoma cells is gamma-linolenic acid deficiency-dependent.

A further critical test of Horrobin's hypothesis that malignancy in cells may be dependent on gamma-linolenic acid (GLA) deficiency, has revealed that GLA supplementation produces a highly significant reduction in the growth rate (up to 87%) of a cultured human hepatoma cell line, compared with the growth rate of untreated hepatoma cells. This supports our previous suggestion that this hypothesis requires urgent further investigation at all levels including trials in human cancer patients.

Antineoplastic Agents↗

The reversibility of cancer: evidence that malignancy in melanoma cells is gamma-linolenic acid deficiency-dependent.

Certain metabolic abnormalities are common to all malignant cells, and Horrobin proposed that the underlying cause is the inability of cancer cells to produce prostaglandin E1 (PGE1). This appears to be due to the lack of the enzyme delta-6-desaturase which converts the essential fatty acid, linoleic acid, to gamma-linolenic acid (GLA), from which PGE1 is then synthesized. Our studies strongly support this contention. Addition to GLA to cancer cells, thus bypassing the block in the metabolic pathway, results in very marked, statistically highly significant inhibition of growth, while having no effect at all on normal cells. Our finding of the regression of cancer through such proposed normalization offers preliminary hope for a new effective and harmless approach to the treatment of cancer.

Animals↗

Dynamic electrocardiography V. The "imaginary cardiac vector" hypothesis: experimental evaluation.

This paper experimentally evaluates the "imaginary cardiac vector" hypothesis, that the cardiac vector is not a real vector. We have previously shown on theoretical grounds that the basis of the cardiac vector is invalid in that Einthoven used scalar, not vector, procedures. Attempts by subsequent workers to compensate for the theoretical flaws have not succeeded. The concept of the "cardiac vector" which they have invented has the dimensions of an imaginary entity. Experimental measurement of isopotential maps derived from dipoles in a volume conductor demonstrates that these dipoles do not summate vectorially. Isopotential maps of the thoracic surface confirm that this applies to the human ECG. An imaginary "man-frog" cardiac vector loop is demonstrated using a lead from a man and a lead from a frog. This illustrates that the "imaginary cardiac vector" is a tenable concept. Finally, a crucial test of the hypothesis is reported which demonstrates that exercise causes deviations of the so-called cardiac vector in opposite directions, simultaneously, in different VCG lead systems. Since a physical entity can only be in one place and more in one direction at a particular instant, this experiment invalidates the "real cardiac vector" hypothesis. This strongly suggests that the cardiac vector is a brilliant, but imaginary, construction with immense clinical value, especially in the interpretation of the sequence of depolarization. Nevertheless, it obstructs analysis of the real basis of the electricity of the heart.

Animals↗

Dynamic electrocardiography. III. The "imaginary cardiac vector" hypothesis: theoretical basis.

The "imaginary cardiac vector" hypothesis states that the "cardiac vector" is not a "real" vector entity. The hypothesis arises from the fact that voltage is not a vector but a scalar quantity. Nevertheless, in classical electrocardiographic analysis and teaching, the ECG voltage is treated as a vector. These voltages are used as "vector" components--first, to calculate a "resultant manifest potential difference", represented by the "cardiac vector" arrow in electrocardiography, and second, to draw the "cardiac vector" loop in vectorcardiography. The resultant "cardiac vector" is usually considered to be a "real" vector quantity describing the electrical activity of the heart. It is also widely believed that this "vector" was first described by Einthoven in 1913. To evaluate the hypothesis, we have utilised the actual values and methods presented by Einthoven, and demonstrated that the theoretical basis of the "cardiac vector" is false. It appears that Einthoven followed scalar and not vector procedures and that he did not describe a vector.

Electrocardiography↗

Creatine phosphokinase and lactate dehydrogenase levels after ultra long-distance running. An analysis of iso-enzyme profiles with special reference to indicators of myocardial damage.

Blood samples obtained from 20 runners on completion or partial completion of a 160-km marathon were assayed for total serum creatine kinase (CK) and lactate dehydrogenase (LD), as well as for the respective iso-enzymes. Total CK was significantly elevated in all subjects, the mean value (2 243 U/l) constituting a 24-fold increase above the normal upper limit. In 65% of these cases, the cardiac-specific iso-enzyme of CK, MB, was present. The mean LD level (1 220 U/l) also exceeded the upper limit of normal significantly, 5 subjects presenting a 'flipped' LD pattern (LD1 greater than LD2). Three subjects exhibited the MB iso-enzyme in the presence of a flipped LD pattern. No electrocardiographic evidence of irreversible cardiac 'damage' could, however, be established after the race, nor any significant decrease in the Bruce protocol stress test rating. It is concluded that the MB iso-enzyme of CK, even in conjunction with a flipped LD pattern, may not represent unequivocal evidence of myocardial damage under all circumstances.

Adult↗

The effect of long-term use of cimetidine on the ultrastructure of gastric parietal cells in man.

The effect of long-term cimetidine therapy on the ultrastructure of human parietal cells was investigated in 2 subjects. It was found that after cimetidine therapy for 1 year: (i) the ultrastructural appearance of the parietal cells was normal, and (ii) the parietal cells responded normally to stimulation by pentagastrin. Evidence in favour of a membrane flow mechanism involved in acid secretion is presented.

Cimetidine↗

Ultrastructure of duodenal epithelial cells in patients with active duodenal ulcers and after treatment with cimetidine.

Comparative ultrastructural studies were conducted on biopsy specimens taken under direct vision by endoscopy from the normal duodenum, from the edge of deep and flat duodenal ulcers, and from areas 1 cm away from such ulcers. In addition, the ultrastructure of biopsy tissue from the scar of ulcers which healed after 6 weeks' therapy with the histaminastructural studies of tissue form the edge of both flat and deep duodenal ulcers showed gross pathological changes, particularly with regard to microvilli. Cells from the edge of deep ulcers showed increased secretory activity. Epithelial tissue 1 cm from flat duodenal ulcers exhibited ultrastructural changes far more severe than cells 1 cm from deep duodenal ulcers. The epithelial tissue from the scar area after 6 weeks' treatment appeared capable of regaining a fully functional role, although it was not normal in all specimens.

Cicatrix↗