Vitamins and intelligence tests.
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Biomedical subjects
Publications and source records attributed to L Pauling.
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Two large-scale studies of the effect of different amounts of L-ascorbic acid in the food on tumor-free survival have been conducted. One involved the incidence of spontaneous mammary tumors in RIII mice, with seven ascorbic acid and three control groups, 50 mice per group. With increasing ascorbic acid in the diet, there was a highly significant delay before appearance of the first tumor. Median age at first tumor was 82.5 wk in ad libitum controls, 124.9 wk in the highest-dose ascorbate group. The proportion of mice with tumors was also reduced. The other study involved dermal neoplasms in mice irradiated with ultraviolet light. A pronounced effect of vitamin C in decreasing the incidence and delaying the onset of malignant lesions was observed with high statistical significance. By 20 wk approximately five times as many mice had developed serious lesions in the zero-ascorbate as in the high-ascorbate group.
The concept that lipoprotein(a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wound healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms of atherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.
We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.
Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis.
The Hardin Jones principle states that for a homogeneous cohort of cancer patients the logarithm of the fraction surviving at time t has a constant slope. With use of this principle, the survival times of the members of a heterogeneous cohort can be analyzed to divide the cohort into subcohorts with different mortality rate constants. Probable values of the additional survival time can be estimated for members surviving at the closing date of a clinical trial, permitting them to be included in the biostatistical analysis of the results of the trial in a more significant way than through Kaplan-Meier renormalization.
With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain.
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A study of the effect of different amounts of L-ascorbic acid (vitamin C), between 0.076% and 8.3%, contained in the food has been carried out with ten groups of RIII mice (seven ascorbic acid and three control groups), with 50 mice in each group. With an increase in the amount of ascorbic acid there is a highly significant decrease in the first-order rate constant for appearance of the first spontaneous mammary tumor after the lag time to detection by palpation. There is also an increase in the lag time. The mean body weight and mean food intake were not significantly different for the seven ascorbic acid groups. Striking differences were observed between the 0.076% ascorbic acid and the control groups (which synthesize the vitamin): smaller food intake, decreased lag time, and increased rate constant of appearance of the first mammary tumor. This comparison cannot be made experimentally for guinea pigs and primates because the control groups would develop scurvy.
Ascorbate in an aqueous solution is easily oxidized by molecular oxygen in the presence of cupric ion, thus producing reactive oxygen species and exhibiting cytotoxicity. In order to increase the antitumor activity of ascorbate, we used the innocuous form of cupric ion complexed with glycylglycylhistidine, a tripeptide designed to mimic the specific Cu(II) transport site of albumin molecule. Although this square planar copper:glycylglycylhistidine complex did not significantly oxidize ascorbate at pH 7.4, it killed Ehrlich ascites tumor cells in vitro in a high concentration of ascorbate. The injections of large doses of ascorbate together with copper: glycylglycylhistidine prolonged the life span of mice inoculated i.p. with Ehrlich tumor cells. The target specificity against tumor cells was primarily attributable to their high peptide-cleaving activity.
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A simple theory of the diamagnetic anisotropy of noncyclic planar groups of atoms with resonance structures (mobile electrons)leads to the value --5.36 x 10(-6) cm-g-sec electromagnetic units for the molar diamagnetic anisotropy of the peptide group.