The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease.

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SUMMARY : Histidine-independent (h+) mutants induced in histidine-requiring (h-) cultures by ultraviolet light have a delay in the onset of logarithmic increase that is about two generations longer than the delay shown by marked unirradiated . h+ bacteria present a t the same time. This extra delay is interpreted as being due to the segregation of one from four nuclei which are present, on the average, in growing h-organisms. The same assumption accounts for the extra delay observed in spontaneous h+ mutahts. These and other results are discussed in relation to the site of mutation and to the various types of delay that can retard the onset of growth of a mutant clone. It is concluded that in the mutation from h-to h+, the h+ condition is dominant in the heterocaryon, that whatever phenotypic delay exists is short, and that cell division is not required to pass through it.In the previous paper (Ryan & Wainwright, 1954) evidence was presented that led to the conclusion that growing Escherichia coli organisms have their genetic material represented at least 4 times, on the average, in each bacterium. In histidine-dependent (h-) bacteria, the mutation leading to a histidine-independent condition (h+) occurs independently among members of each set. Thus bacteria are produced which are initially heterocaryotic. Only after growth and division does the heterocaryon segregate its nuclei so that a homocaryotic mutant offspring is produced and only then does the clone of mutants increase by doubling. This delay is referred to as segregation lag and, in the system studied, lasted for a minimum of two generations. The evidence came from the overall rate of increase of mutants in growing populations of mutating parental bacteria and was therefore indirect. It seemed desirable to perform experiments with populations in which a large crop of new mutants had just been induced. The number present would not be expected to increase until they had become homocaryotic by the segregation of their non-mutant nuclei during growth. The length of the delay would be a function of the average number of nuclei per bacterium according to the relation : log no. of nuclei/bacterium generations of segregation lag = log 2 This possibility was approached directly by exposing h-bacteria to ultraviolet light until more than 90% of the h+ mutants present were induced mutants. The culture was then spread on the surface of agar devoid of histidine where only the h+ mutants were able to grow and form colonies. From time to time the surfaces were re-spread in a way that separated all of the growing bacteria present. Only after segregation lag was over did the number of h+ colonies increase. Since the irradiated culture had to be washed in order to remove histidine from the h-parents and prevent their growth, and had to be

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A variety of methyl donor compounds, such as choline and betaine, are known to be sources of the methyl group of methionine when this compound is synthesized by animal tissues (du Vigneaud, 1952). However, none of the known transmethylation reactions has been shown to occur in the bacterial synthesis of methionine. In the first paper in this series (Shapiro, 1953) it was shown that thiomethyladenosine could support the growth of certain methionine auxotrophs of Aerobacer aerogenes. The mechanism of utilization of thiomethyladenosine by one of these mutants has been investigated further. The results to be presented here suggest a new pathway of biosynthesis of methionine by this organism and indicate that thiomethyladenosine is a precursor of the thiomethyl group of methionine. MATERIAL AND METHODS Cultural mwthods. Aerobacter aerogenes, strain NRRL 199, was used as the parent strain, Culture 68, which requires methionine or thiomethyladenosine for growth, was used in this study. The isolation of the mutant and the cultural procedures used have been described previously (Shapiro, 1953). All chemicals used were commercial products except thiomethyladenosine and thiomethylribose which were generously supplied by Dr. F. Schlenk. Preparation of labeled thiomethyladenosine. Schlenk and Smith (1953) have shown that the thiomethyl group of methionine is transferred to thiomethyladenosine in yeast cells. Therefore, DL-methionine-S'3 or D-methionine-C04H32 was added to a culture of Torulop8is utilis in order to obtain 35" or C14H3 labeled thiomethyladeno