O2-alkylcytidine--a new major product of neutral, aqueous reaction of cytidine with carcinogens.
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Biomedical subjects
Publications and source records attributed to B Singer.
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1. The effect of low-frequency stimulation of the renal nerves on renal function and renin release has been investigated. The experiments were performed in unilaterally nephrectomized, anaesthetized cats in which the nerves to the remaining kidney were sectioned. 2. When stimulation frequency was adjusted to reduce renal blood flow by approximately 15% for 15 min, glomerular filtration rate was hardly affected. The ratio sodium clearance/glomerular filtration rate was significantly reduced and plasma renin activity was significantly increased. 3. When the renal nerves were similarly stimulated in the presence of the beta-adrenergic receptor blocking agent, propranolol, the glomerular filtration rate was significantly reduced and the rise in plasma renin activity was significantly inhibited. The reduction of sodium clearance/glomerular filtration rate was as great as in the control animals. 4. The results are consistent with the view that the maintenance of glomerular filtration rate, during renal nerve stimulation which reduced renal blood flow, may be mediated by the local generation of angiotensin. The results also suggest that angiotensin does not play an important role in the sodium retention associated with increased renal nerve activity.
In non-aqueous solution, diazomethane and diazoethane react with the O2, O4 and N-3 sites of uridine, thymidine, 1-methyluracil and 1-methylthymine. Diazoethane has a higher affinity for alkylating oxygens than does diazomethane. The relative ratio of O2:O4:N-3 methyl products is 1:2:16 and of ethyl products the ratio is 1:1:2. When the diazoethane reaction is performed in neutral buffered solution, the same proportion of O2:O4:N-3 ethyl products is found, but the extent of reaction is very low. O2-alkylation greatly labilizes the glycosidic bond of thymidine and uridine toward acid hydrolysis. All O2 and O4 alkyl 1-substituted 2,4-dioxopyrimidines are dealkylated in weak acid but the O2 alkyl group is the more stable.
Early recognition, adequate treatment, close observation, and systematic follow-up over a long period are essential to renal salvage in the child with vesicoureteral reflux. The decision whether and when to operate is made on a balance of factors by the pediatrician-urologist team. Among 236 patients with reflux diagnosed during childhood, reflux was stopped in 55 per cent of those treated medically and in 98 per cent of the more severe cases who were treated by ureteral reimplantation. Chronic pyelonephritis appeared or worsened during medical management in 12 per cent; no child showed new pyelonephritic scars or worsening of pyelonephritis after ureteral reimplantation.
A case of recurrent polyradiculoneuritis in a 54-year-old man is described. It is exceptional because of its lengthy development over a period of 19 years and by its association with a paraprotein of the IgE type without anyother anomal. Corticotherapy had a favourable effect on the clinical symptoms but did not affect the amount of monoclonal immunoglobulin in the serum. The nosological position of this neuropathy and the type of gammapathy are discussed. An immune mechanism seems likely, but no proof of a link between the neuropathy and the gammapathy could be found.
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At pH 6.8 in aqueous solution (4 hr, 22 degrees), all methylating agents tested, i.e., dimethyl sulfate, methyl methanesulfonate, and methylnitrosourea, react with both the N-3 of the ring and the phosphate of UMP and dTMP. Although the extent of reaction varies from 17 to 76%, the ratio of phosphate/ring methylation is approximately 4. Both the 3-methyl nucleotides and methyl ester of 3-methyl nucleotides are identified, as well as the methyl esters of unmodified UMP and dTMP. At pH 8.2 the extent of total methylation is similar but reactivity of the N-3 is increased and that of the phosphate decreased so that the phosphate/ring ratio is approximately 1. At pH 6 almost all reaction is with the phosphate group. Uridine, under the same conditions, is methylated at pH 6.8 to form 15% 3-methyluridine and, at pH 8.2, the N-3 of uridine and thymidine is methylated to about 50%. Neither uridine nor UMP forms detectable ribose methyl products at any of these pH's. The comparable ethylating agents (diethyl sulfate, ethyl methanesulfonate, and ethylnitrosourea) are less reactive and the total ethylation of UMP or dTMP is about 1/5 that of methylation. There is little ethylation of the N-3 but the phosphate is alkylated to a relatively high extent so that the phosphate/base ratio at pH 6.8 is 10-23, and at pH 8.2 the ratio is 5-8. The fact that ethylating agents have a greater affinity than methylating agents for alkylating phosphates is proposed as the basis for the previously reported analytical data in which ethylating agents, acting on DNA or RNA at neutrality, form more phosphotriesters than the analogous methylating agents.
The sites and extent of ethyl products of neutral ethylation of HeLa cell DNA by [14-C]diethyl sulfate, [14-C]ethyl methanesulfonate, and [14-C]ethylnitrosourea have been determined in vitro and in vivo, and found to differ significantly depending on the ethylating agents. Diethyl sulfate and ethyl methanesulfonate ethylate the bases of HeLa cell DNA in the following order: 7-ethylguanine greater than 3-ethyladenine greater than 1-ethyladenine, 7-ethyladenine greater than 3-ethylguanine, 3-ethylcytosine, O-6-ethylguanine. Ethyl bases accounted for 84-87% of the total ethyl groups associated with HeLa cell DNA. Ethylnitrosourea, in contrast, has particular affinity for the O-6 position of guanine. It ethylates the bases of HeLa cell DNA in the following order: O-6-ethylguanine, 7-ethylguanine greater than 3-ethyladenine greater than 3-ethylguanine, 3-ethylthymine greater than 1-ethyladenine, 7-ethyladenine, 3-ethylcytosine. Ethylation of the bases only accounts for 30% of the total ethylation in the case of ethylnitrosourea. The remaining 70% of the [14-C]ethyl groups, introduced in vivo and in vitro, are in the form of phosphotriesters which after perchloric acid hydrolysis are found as [14-CA1ethanol and [14-C]ethyl phosphate. In contrast, phosphotriesters amounted to only 8-20% of total ethylation in in vivo or in vitro diethyl sulfate and ethyl methanesulfonate treated HeLa cell DNA, and 25% of the total methylation in in vitro methylnitrosourea treated HeLa cell DNA. Alkylation at the N-7 and N-3 positions of purines in DNA destabilizes the glycosidic linkages. Part of 7-ethylguanine and 3-ethyladenine are found to be spontaneously released during the ethylation reaction. Incorporation of the 14-C of the alkylating agents into normal DNA bases of HeLa cells can be eliminated by performing the alkylations, in the presence of cytosine arabinoside, for 1 hr.
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A total of 495 African infants of low birth weight were discharged from Harari Maternity Hospital, Salisbury, between October 1972 and September 1973. Criteria used for discharge were (a) no clinical evidence of disease, (b) satisfactory feeding by mouth (breast or bottle or both), and (c) stable temperature control under normal room conditions. Of the 495 babies 264 fulfilled these criteria when they weighed 1801-1900 g (group 1), 99 when they weighed 1901-2000 g (group 2), and 132 (group 3) when they weighed 2001-2500 g. The overall follow-up rate of those infants living in greater Salisbury was 85-5%, the health visitor playing an important contributory role in their progress, especially those in group 1. More than two clinic visits in the first four to five weeks after discharge were essential for continuing weight gain in groups 1 and 2 but not in group 3. The mean daily weight gain for all babies at the end of four to five weeks was 26 g. Readmission rates for babies in groups 1,2, and 3 were 9-5%, 1%, and 0-8%, respectively, the largest single cause for readmission being bronchopneumonia associated with hypothermia. Altogether 60% of the readmissions occurred during the two winter months (June and July). Hypothermia, associated with low environmental temperatures played a significant part in morbidity and mortality, and twins, particularly in group 1, had a mortality rate three times greater than singletons in the same group. In general, even in underdeveloped communities singleton babies born outside the winter months with reasonable clinic or home visiting facilities can be discharged at a weight of 1800 g or more.
Tallies were made of outcomes of all resonably controlled comparisons of psychotherapies with each other and with other treatments. For comparisons of psychotherapy with each other, most studies found insignificant differences in proportions of patients who improved (though most patients benefited). This "tie score effect" did not apply to psychotherapies vs psychopharmacotherapies compared singly-psychotherapies did better. Combined treatments often did better than single treatments. Among the comparisons, only two specially beneficial matches between type of patient and type of treatment were found. Our explanations for the usual tie score effect emphasize the common components among psychotherapies, especially the helping relationship with a therapist. However, we believe the research does not justify the conclusion that we should randomly assign patients to treatments-research results are usually based on amount of improvement; "amount" may not disclose differences in quality of improvement from each treatment.
The effects of attention and reading tests on the EEG and the H reflex were studied in a patient affected by primary reading epilepsy. During the attention tests, EEG was normal while H reflex was facilitated. On the contrary, during reading tests, EEG showed typical epileptic seizures while at the same time, the H reflex was depressed.
Upon ethyl nitrosourea treatment of RNA of tobacco mosaic virus, up to four phosphodiester groups may be alkylated per molecule without chain breakage, as shown be sucrose gradient centrifugation. This indicates that ribophosphotriesters are quite stable. However, when this alkylation reaction is of longer duration and 6 to 10 triesters are formed, then an average of 1 to 2 breaks occurs and little or no intact RNA can be isolated. Methyl nitrosourea is less effective in forming triesters (about 25% of total alkyl groups compared to about 65% for ethyl nitrosourea), and a greater number of alkyl groups can, therefore, be introduced before breaks occur. Diethyl sulfate and dimethyl sulfate, which alkylate almost only the bases of nucleic acids, do not cause significant degradation of RNA of tobacco mosaic virus, even when as many as 70 alkyl groups are bound. All types of alkylation cause similar losses in viral infectivity at low levels of alkylation. Thus, an average of two chemical events leads to one lethal event, regardless of the nature of the alkylating reaction, which, for example, is with dimethyl sulfate about 65% on the N-7 guanine while with ethyl nitrosourea it is about 65% on phosphodiesters. It is thus concluded that all alkyl groups, whether on the base or on the phosphate, have the same potential to cause inactivation and that inactivation of RNA can result from phosphotriester formation per se.
1 Isolated renal cortical cells of the cat have been demonstrated to produce renin on incubation in vitro. After 2 h of incubation, without added agonist, the total amount of renin in the flask increased by a mean of 27.2 percent. The increase in renin content of the incubation flask was found to be present in the medium. 2 Noradrenaline (1.18 times 10-minus 4M) and adrenaline (1.09 times 10-minus 4M) added to the incubation medium stimulated renin production by 45 and 34% respectively, compared with the incubated controls. Most of the increase in renin production was present in the incubation medium. 3 Isoprenaline did not stimulate renin production. However, when added to the incubation medium at a concentration of 0.72 times 10-minus 4M there was a significant decrease in the cellular content and a significant increase in the medium content of renin. This increase was at least as great as that observed with adrenaline and noradrenaline. 4 Salbutamol had an effect similar to isoprenaline, i.e. it induced the release of renin into the medium without affecting production. In this respect it was about a third as potent as isoprenaline.
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