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Biomedical subjects

W Warren

Publications and source records attributed to W Warren.

At least 73 records · Page 4Linked to original sources
PubMed1982

Acute pyelonephritis in the elderly.

We did a prospective study of the clinical, laboratory, radiologic, and therapeutic features of acute, symptomatic, bacterial pyelonephritis in 35 consecutive elderly, noncatheterized patients who required hospitalization. Pyelonephritis had been identified as the most common cause of gram-negative bacteremia in elderly patients admitted to a community hospital. Appropriate antibiotic therapy and, of equal importance, a lack of serious associated medical illnesses contributed to the 97% survival. Two features appear to distinguish acute, symptomatic, bacterial pyelonephritis in elderly women from that in young women: an increased incidence of bacteremia and septic shock. We provide guidelines for the diagnostic evaluation and antibiotic therapy of acute, symptomatic, community-acquired, bacterial pyelonephritis in the elderly.

Acute Disease↗
PubMed1982

Symptomatic pyelonephritis in elderly men.

A prospective study was carried out of the clinical, laboratory, radiologic and therapeutic features of acute, symptomatic, bacterial pyelonephritis as experienced by 12 consecutive elderly, noncatheterized men who required hospitalization. In spite of the advanced ages of the men and the inordinate frequency of bacteremia and septic shock, no patient died. "Appropriate" antibiotic therapy, supportive treatment, and, as importantly, a lack of associated "imminently" or "ultimately" fatal illnesses contributed to the 100 per cent survival rate. Guidelines are provided for the diagnostic evaluation and antibiotic therapy of community-acquired pyelonephritis in elderly men.

Aged↗
PubMed1982

Atypical oculomotor paresis.

A series of patients is presented with partial oculomotor palsies. The accompanying signs of neurologic dysfunction are indicative of a mesencephalic lesion. The peculiar anatomy of the third cranial nerve permits one to infer precise localization of the lesions.

Adolescent↗
PubMed1982

Defluorination of methoxyflurane by glutathione and coenzyme B12.

Fluoride was eliminated from methoxyflurane in solutions which contained glutathione and coenzyme B12. The reaction rate was maximal at pH 10 and was dependent upon the concentration of each reactant under specified conditions. A stoichiometric ratio of 2 was found between the amount of glutathione utilized and the amount of fluoride generated in the reaction. Glutathione disulfide was the only stable ninhydrin-positive reaction product identified.

Cobamides↗
PubMed1980

Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification.

The carcinogenic potency of simple aliphatic alkylating agents such as the alkylnitrosamides and the alkylmethanesulphonates is positively correlated with their ability to alkylate the relatively weakly nucleophilic oxygen atoms in DNA, particularly the O6-atom of guanine. Differences in the spectrum of DNA alkylations produced by these agents can be rationalised on chemical grounds in that the electrophilic reactivity of the alkylating species determines the extent to which it will react at sites of weaker nucleophilicity. Alkylation of the more strongly nucleophilic ring nitrogen atoms of the purine bases, which is the main site of reaction with all these agents, appears to be much less important in alkylation carcinogenesis. O6-alkylation of guanine is likely to interfere with DNA base-pair hydrogen bonding and is possibly the major DNA modification responsible for the induction of GC yields AT transition mutations in bacteria and bacteriophage by alkylating agents. Here, we have studied the effects of three methylating agents of contrasting carcinogenic potency on mammalian (V79 Chinese hamster) cells in in culture. We report that the mutagenicity but not the cytotoxicity of each agent reflects its carcinogenicity and, furthermore, that the marked differences in mutagenicity are closely paralleled by differences in levels of O6-guanine methylation.

Alkylating Agents↗
PubMed1979

The stability of methylated purines and of methylphosphotriesters in the DNA of V79 cells after treatment with N-methyl-N-nitrosourea.

V79-379A cells growing in suspension culture were treated with N-methyl-N-nitrosourea at concentrations of 0.6 and 1.2 mM. After incubation for periods from 1 to 48 h DNA was isolated from the cells and the concentrations of 7-methylguanine, O6-methylguanine, 3-methyladenine and methyl phosphotriesters were determined. After correction for dilution resulting from DNA synthesis during the incubation it was found that no loss of O6-methylguanine or methylphosphotriesters occurred; 7-methylguanine disappeared with a half-life of 22 h and 3-methyladenine was detectable only immediately after the initial treatment. The results show that these cells eliminate 7-methylguanine and 3-methyladenine from DNA by a repair process but are unable to excise or repair O6-methylguanine or methyl phosphotriesters.

Adenine↗
PubMed1979

Physicians and death: some Australian data.

Despite a significant interest in bereavement in this country there are little hard data on attitudes to, beliefs about, and experiences with, death and dying in the Australian context. This paper reports the results of a survey in the area with special reference to the responses of medical practitioners and medical students.

Attitude to Death↗
PubMed1979

The excision of N-methyl-N-nitrosourea-induced lesions from the DNA of Chinese hamster cells as measured by the loss of sites sensitive to an enzyme extract that excises 3-methylpurines but not O6-methylguanine.

An enzyme extract from Micrococcus luteus excises 3-methyladenine and 3-methylguanine but not O6-methylguanine, 7-methylguanine, 1-methyladenine or 7-methyladenine from DNA reacted with N-methyl-N-nitrosourea. The extract was used to detect lesions in the DNA of Chinese hamster cells treated in culture with N-methyl-N-nitrosourea. It was concluded that 3-methyladenine is excised from these cells with a half-life of about 2.3 h.

Animals↗
PubMed1978

Alkylation of deoxyribonucleic acid in vivo in various organs of C57BL mice by the carcinogens N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea and ethyl methanesulphonate in relation to induction of thymic lymphoma. Some applications of high-pressure liquid chromatography.

1. Methods were developed for analysis of alkylpurines, O2-alkylcytosines, and representative phosphotriesters [alkyl derivatives of thymidylyl(3'-5')thymidine], in DNA alkylated in vivo, using high-pressure liquid chromatography. 2. The patterns of alkylation products in DNA in vivo at short times were closely similar to those found for reactions in vitro. Alkylation by the nitrosoureas was complete in vivo within 1 h, but with ethyl methanesulphonate was maximal at 2--4h. 3. The time course of persistence of alkylation products in vivo was determined for several tissues. In addition to the rapid loss of 3- and 7-alkyladenines reported previously for all tissues, a relatively rapid loss of O6-alkylguanines from DNA of liver was found which was more rapid at lower doses. In brain, lung and kidney, excision of O6-alkylguanine was much less marked, but was not entirely excluded by the data. In thymus, bone marrow and small bowel, all alkylated bases were lost with half-lives of 12--24h, at non-cytotoxic doses of alkylation. 4. No evidence for any marked excision of other minor products from alkylated DNA in vivo was found; thus 1-methyladenine, O2-ethylcytosine (found in appreciable amount only with N-ethyl-N-nitrosourea), 3-methylguanine, and dTp(Alk)dT persisted in alkylated DNA, including DNA of liver. 5. The induction of thymic lymphoma was determined over the range of single doses by intraperitoneal injection up to about 60% of the LD50 values, and related to the extent of alkylation of target tissues thymus and bone marrow. With N-methyl-N-nitrosourea over 90% tumour yield was attained at 60 mg/kg, and with N-ethyl-N-nitrosourea up to 52% at 240 mg/kg, but with ethyl methanesulphonate at up to 400 mg/kg only a few per cent of tumours were obtained. 6. The carcinogenic effectiveness of the agents was positively correlated with the extents of alkylation of guanine in DNA of target tissues at the O-6 atom. On the basis that at doses giving equal carcinogenic response these extents of alkylation would be equal, the chemical analyses showed that the ratio of equipotent doses to that for N-methyl-N-nitrosourea would be, for N-ethyl-N-nitrosourea, 5.3 for ethyl methanesulphonate about 21, and for methyl methanesulphonate [Frei & Lawley (1976) Chem.-Biol. Interact. 13, 215--222] about 144. These predictions were in reasonably good agreement with the observed dose-response data for these agents.

Alkylation↗
PubMed1976

Removal of minor methylation products 7-methyladenine and 3-methylguanine from DNA of Escherichia coli treated with dimethyl sulphate.

Persistence of methylpurines in DNA methylated in vitro and in vivo in Escherichia coli WP2 cells, by dimethyl sulphate (DMS) was studied, with particular reference to the minor products 7-methyladenine and 3-methylguanine, not previously investigated in this respect, but known to be removed from DNA in vitro by spontaneous hydrolysis at neutral pH. The half-life of 7-methyladenine in vivo was relatively short (2.6 +/- 0.2 h) but not significantly shorter than in vitro at pH 7.2, 37 degrees C. The half-life of 3-methylguanine was 3.6 +/- 0.3 h in vivo, markedly shorter than in vitro, where its stability was somewhat greater than that of 7-methylguanine. Enzymatic excision of 3-methylguanine was therefore indicated to occur in E. coli. Previous findings that 7-methylguanine is probably not enzymatically excised from DNA in vivo, whereas 3-methyladenine is rapidly removed, were confirmed, and additional support for the concept of enzymatic removal of 3-methyladenine was obtained by showing extensive inhibition of its removal from cells treated with iodoacetamide prior to methylation. It is suggested that methylations of adenine or guanine in DNA at N-3 constitute blocks to template activity of DNA and stimulate a "repair" response of enzymatic removal of 3-methylpurines. Possible valence bond structures for 3-methylpurine residues in DNA are discussed, leading to the suggestion that ionized forms with positively charged amino groups may be the most effective blocks to template activity.

Adenine↗