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Biomedical subjects

B Singer

Publications and source records attributed to B Singer.

At least 37 records · Page 2Linked to original sources
PubMed1977

Sites in nucleic acids reacting with alkylating agents of differing carcinogenicity of mutagenicity.

The site of alkylation of a nucleic acid, in vivo, is greatly dependent on the type of alkylating agent. Most alkylating agents of low mutagenicity or carcinogenicity (such as dimethylsulfate) react primarily with the ring nitrogens. The carcinogenic N-nitroso compounds have a great affinity for alkylating oxygens and react with all ring oxygens as well as the phosphodiesters and, in the case of RNA, with the 2'-O of ribose. Ethylating agents, though in absolute terms less reactive than the corresponding methylating agents, show even greater affinity toward oxygens. It appears that the ethyl nitroso compounds that are carcinogenic are also the most reactive with oxygens.

Alkylating Agents↗
PubMed1977

The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo.

1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1976

All oxygens in nucleic acids react with carcinogenic ethylating agents.

Over 80% of ethylnitrosourea and ethylnitrosoguanidine modification of nucleic acids is on oxygens. The reactivity of oxygens (other than ribose and phosphate) in single-stranded RNA is: O2 of C greater than O2 of U greater than O6 of G greater than O4 of U. In double-stranded DNA the order is: O2 of T equals O6 of G greater than O4 of T greater than O2 of C. Oxygen reactivity of single-stranded DNA resembles RNA. The glycosidic bond of O2-alkylpyrimidines is labilised.

Alkylation↗
PubMed1976

Alkylation of ribose in RNA reacted with ethylnitrosourea at neutrality.

Ribose oxygens in TMV-RNA are ethylated by the carcinogen ethylnitrosourea in neutral aqueous solution (pH 6.1-7.3). 2'-O-ethyluridine, and 2'-O-ethylcytidine have been identified as reaction products. The four 2'-O-ethyl nucleosides are found in approximately equal amounts and the total extent of ribose alkylation is about 15% of the total ethylation. This finding, in conjunction with earlier results showing that all ring and phosphate oxygens can be ethylated, signifies that every oxygen in RNA or polyribonucleotides can react with ethylnitrosourea. The possible biological significance of ribose alkylation, resulting from chemical rather than enzymatic reaction, is discussed. The preparation of the new derivative 2'(3')-Oethylguanosine is described.

Alkylation↗
PubMed1976

Sites of alkylation of poly(U) by agents of varying carcinogenicity and stability of products.

Several alkylating agents of widely varying reported carcinogenicity (dimethylsulfate, diethylsulfate, ethylmethanesulfonate, methylnitrosourea, ethylnitrosourea and ethylnitrosoguanidine) were reacted with poly(U) at pH values ranging from 4.5 to 7.5. All nucleophilic centers (internal phosphate groups, ribose hydroxyls, and O2, N-3 and O4 sites of the uracil base) were found reactive, though to different extents, at neutrality and in slightly acid solution. The distribution of products is a function of the alkylating agent and pH. The nitroso compounds are more reactive toward oxygens than are dialkylsulfates and alkylalkanesulfonates. The ratio of N : O alkyl products is strongly pH dependent, primarily due to the N-3 being most reactive at the higher pH values, while the diester is most reactive at the lower pH values. The extent of reaction of the O2, O4 or 2'-O or ribose is not greatly affected over the pH range tested. At pH 5.0 alkyl ribophosphotriesters mainly lose alchol to re-form a stable phosphodiester. With increasing OH- concentration, the favored reaction is chain scission at the 3'-O-P bond.

Alkylating Agents↗
PubMed1976

[Circulatory disorders induced by amantidine].

Amantadine has been used since 1969 in the treatment of Parkinson's disease. In 1970, were described the special symptoms noted in the lower limbs due to this drug. The authors, after a review of the various disturbances, have studied 10 cases by Capillaroscopy. They emphasize the interest of the study of this abnormality of the micro-circulation, producing vaso-constriction of the arterioles and venules.

Aged↗
PubMed1976

The sodium-retaining effect of renal nerve activity in the cat: role of angiotensin formation.

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.

Aminohippuric Acids↗
PubMed1976

Reaction of diazoalkanes with 1-substituted 2, 4-dioxopyrimidines. Formation of O2, N-3 and O4-alkyl products.

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.

Alkanes↗
PubMed1976

The practical management of vesicoureteral reflux in children. A review of 12 years' experience with 236 patients.

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.

Adolescent↗
PubMed1976

[Recurrent polyneuropathy with a 19-year course, associated with a benign IgG monoclonal gammapathy].

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.

Bone Marrow↗
PubMed1975

Methylation and ethylation of uridylic acid and thymidylic acid. Reactivity of the ring and phosphate as a function of pH and alkyl group.

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.

Chemical Phenomena↗
PubMed1975

The specificity of different classes of ethylating agents toward various sites of HeLa cell DNA in vitro and in vivo.

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.

Binding Sites↗