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Biomedical subjects

R Cox

Publications and source records attributed to R Cox.

At least 181 records · Page 10Linked to original sources
PubMed1984

Can nocturnal emergency surgery be reduced?

A prospective study of emergency operations was performed over three months in a district general hospital. Before starting surgery surgeons completed a questionnaire recording clinical details together with time of admission and were asked to state whether in their opinion the case could be safely deferred until the next morning assuming operating time was available. Of 251 operations performed, forms were completed for 244. According to the surgeons, 62 could have been safely deferred, and subsequent independent analysis indicated a further 24 could also have been safely postponed, giving a total of 86 cases (35%). Of the remainder, 71 were started between 2300 and 0900, and of these 51 (71%) were major operations requiring an experienced surgeon. The results suggest that, although the volume of nocturnal major surgery could not be reduced, the introduction of a daily emergency theatre session for cases seen during the day and those which could be deferred from the previous night would appreciably reduce the overall workload of nocturnal surgery at present done by the resident junior staff. This study will have important implications if, as has been suggested, the number of junior medical staff on call at night for emergencies is reduced.

Emergencies↗
PubMed1984

DNA-mediated gene transfer into human diploid fibroblasts derived from normal and ataxia-telangiectasia donors: parameters for DNA transfer and properties of DNA transformants.

We investigate the feasibility of DNA-mediated gene transfer into human diploid fibroblasts derived from patients with the radiation sensitive syndrome ataxia-telangiectasia (A-T) and from a normal donor. Although they are markedly different in their growth characteristics, both normal and A-T strains give similar frequencies for DNA transfer in a model system using the recombinant plasmid pSV2 -gpt. pSV2 -gpt DNA transformants arise with a frequency between 10(-5) and 10(-4) per viable cell. Analysis of such transformants, although possible, is severely handicapped by the limited clonal life span of diploid human cells. Despite these problems it may be concluded that diploid human fibroblasts are competent recipients for DNA-mediated gene transfer and the putative repair deficiency of A-T does not markedly effect the efficiency of this process.

Ataxia Telangiectasia↗
PubMed1984

Characterization of the purine ring-opened 7-methylguanine and its persistence in rat bladder epithelial DNA after treatment with the carcinogen N-methylnitrosourea.

Purine ring-opened 7-methylguanine, prepared in vitro by alkaline treatment of 7-methylguanosine or of methylated calf thymus DNA, was extensively characterized by chromatographic and spectral techniques as N5-methyl-N5-formyl-2,5,6-triamino-4-hydroxypyrimidine. This modified base chromatographed as an early-eluting peak on an ion-exchange column but separated into two interconvertible components after reversed-phase or porous-resin h.p.l.c. The two components were analyzed by thermal desorption mass spectrometry and 500 MHz 1H-n.m.r. spectroscopy. Their mass spectra were identical (M+ at m/z 183) and their n.m.r. spectra each exhibited the same two sets of resonances whose relative intensities were solvent-dependent. Analysis by h.p.l.c. showed interconversion of the two components and kinetic studies demonstrated that this reaction was a reversible first-order process. At equilibrium, k1 = k2 = 0.334 h-1 and delta G = 22.9 kcal/mol. These data indicated that the ring-opened 7-methylguanine exists as cis/trans isomers with restricted rotation about the amide bond. Treatment of rats with an intraurethral initiating dose of the carcinogen N-methylnitrosourea resulted in a high level of bladder epithelial DNA modification with 7-methylguanine, O6-methylguanine, and methyl phosphotriesters as major adducts at 2 h after instillation. Purine ring-opened 7-methylguanine, chromatographically identical to the in vitro products, was initially a minor adduct. However, it was the only persistent modification in the bladder epithelial DNA and eventually accounted for 72% of the total carcinogen binding after 21 days. A tumor-promoting regimen, involving dietary sodium saccharin, did not alter the repair or persistence of any of the methylated adducts. These data demonstrate that purine ring-opened 7-methylguanine, previously reported to exist in liver DNA after N,N-dimethylnitrosamine or 1,2-dimethylhydrazine treatment, is present in a carcinogen-target tissue and is considerably more persistent than O6-methylguanine or other DNA methylation products. The possible role of this adduct as a promutagenic lesion initiating urinary bladder carcinogenesis is discussed.

Animals↗
PubMed1984

The use of recombinant DNA plasmids for the determination of DNA-repair and recombination in cultured mammalian cells.

Using the recombinant plasmid pSV2gpt and DNA transfer techniques, cell mediated DNA ligation and recombination of plasmid DNA have been demonstrated in four human cell lines. Data suggesting the involvement of a possible defect in the cellular equilibrium between ligation and exonuclease digestion of double strand DNA scissions in an ataxia-telangiectasia (A-T) cell line is discussed. The same A-T line was grossly proficient in DNA recombination but it will be necessary to distinguish between recombination in coding and non-coding plasmid sequences.

Ataxia Telangiectasia↗
PubMed1984

Synthesis of S-adenosylethionine by the gamma isozyme of methionine adenosyltransferase from Friend erythroleukemic cells.

Methionine adenosyltransferase (adenosine 5'-triphosphate-L-methionine S-adenosyltransferase, EC 2.5.1.6) was found to occur only as the gamma isozyme in Friend erythroleukemic cells. Enzyme activity in a dialyzed 105,000 X g supernatant was linear for at least 30 min and dependent on the amount of protein added. The Km for methionine was 10.6 microM. In the presence of 10% dimethyl sulfoxide, the enzyme activity was slightly inhibited and dithiothreitol was not required for maximum activity. These properties identify the methionine adenosyltransferase in Friend erythroleukemic cells as the gamma isozyme. L-Ethionine served as a substrate with a Km of 30 microM, and competitively inhibited the enzyme activity with a Ki of 150 microM. Friend erythroleukemic cells grown in the presence of ethionine accumulated S-adenosylethionine, which was dose and time dependent. Therefore, the gamma isozyme of methionine adenosyltransferase from Friend erythroleukemic cells utilize L-ethionine as substrate, resulting in an accumulation of S-adenosylethionine. These studies provide a mechanism by which ethionine through S-adenosylethionine may alter the methylation of DNA in Friend erythroleukemic cells.

Animals↗
PubMed1983

Preliminary characterisation of inhibitors of DNA polymerase isolated from Xenopus laevis early embryos.

Inhibitors of DNA polymerase have been detected in Xenopus laevis ovary and egg extracts. The characteristics of the inhibitors differ between the two extracts. In ovary preparations, the inhibitor is retained by dialysis tubing and is heat sensitive, whereas in egg extracts it is diffusable and heat stable. In both extracts, the activity co-elutes with DNA polymerase after ion exchange chromatography. Chromatography of ovary extracts renders the inhibitor diffusable and heat stable. Preliminary characterisation of inhibitory activity from eggs shows that the substance is sensitive to pronase digestion and has an approx. 300-500 molecular weight. Kinetic studies demonstrate that the inhibitor is uncompetitive with the DNA template and show mixed inhibitory kinetics with respect to the deoxynucleotides.

Animals↗
PubMed1983

Nicotinamide methyltransferase inhibition by S-adenosylethionine.

An assay for nicotinamide methyltransferase which uses an Affi-Gel 601 boronate column to separate substrate from product has been used to study the inhibition of the nicotinamide methylase. S-Adenosylethionine and S-adenosylhomocysteine inhibited the enzyme in a dose dependent fashion. Five times more S-adenosylethionine than S-adenosylhomocysteine was necessary for 50% inhibition of the enzyme. Data from a substrate concentration curve supports a competitive type of inhibition for both inhibitors. It is proposed that this inhibition may alter liver levels of nicotinamide and the urinary excretion of N1-methylnicotinamide.

Adenosine↗
PubMed1983

Squamous cell carcinoma of the base of the tongue.

The squamous cell carcinomas of 119 patients treated between 1958 and 1980 were retrospectively reclassified according to the 1977 American Joint Committee for Cancer Staging-End Results Reporting guidelines. Analysis of the information was performed with an interactive computer program that allows the analysis of a large number of medical factors with numerous variables. The following factors show the statistically significant improved survival rates: well-differentiated histopathologic findings, small T-stage lesions, and clinically negative neck disease. Although the survival curve was similar in the planned combined therapy and radiation therapy groups, local control was statistically superior in the combined therapy group. A similar trend is seen in those patients who receive interstitial implants in addition to external beam therapy. A randomized prospective study is needed to determine the optimum mode of therapy.

Adult↗
PubMed1983

A comfortable, minimum stress method of restraint for Yucatan miniature swine.

For comfortable, minimal-stress restraint of Yucatan miniature swine, a heavy cotton duck sling reinforced with nylon webbing and covered with vinyl was used. The sling was designed with four leg openings and one hole for access to the anterior vena cava. Custom padding was used to line the leg holes and minimize chafing. Five sling sizes were developed for the restraint of any size Yucatan miniature pig (3 to 75 kg) or other pigs up to 150 kg. A steel frame on wheels was designed with or without a boat winch crank mechanism to support the interchangeable slings. The pig restraint was accomplished by lifting or hoisting the animal, depending on animal size.

Animals↗
PubMed1982

The effects of radiation therapy for Hodgkin's disease in a child with ataxia telangiectasia: a clinical, biological and pathologic study.

Stage I lymphocyte-predominant Hodgkin's disease was diagnosed in a 44-month-old girl. Although immune deficiency was suspected and IgA deficiency demonstrated, the diagnosis of an ataxia-telangiectasia (AT)-like syndrome was not confirmed until eight weeks later when results of studies on the radiosensitivity of cultured skin fibroblasts were available. The child had none of the usual physical stigmata of AT. Severe acute radiation damage followed the treatment of this child with standard doses of radiation therapy. Clinical, pathologic, and radiobiologic correlations are drawn. The diagnosis of a malignant lymphoma disorder in children under the age of five should alert clinicians to the possibility of immune deficiency and, even in the absence of classical physical signs, to AT in particular. Suggestions for the management of future similar cases are put forward.

Ataxia Telangiectasia↗
PubMed1982

Metoclopramide in the reduction of nausea and vomiting associated with combined chemotherapy.

The nausea and vomiting associated with combination chemotherapy is a serious cause of morbidity. Though widely used, metoclopramide has not previously been shown, in controlled studies, to be of benefit in reducing these side-effects. A double blind placebo-controlled randomized trial of IV and oral metoclopramide is reported, based on 117 courses of chemotherapy. Of 59 courses in which metoclopramide was given, vomiting was prevented in 28 (47%), compared with only 10 of 58 (17%) in the control group, a highly significant (P less than 0.001) improvement. The importance of adequate dosage of metoclopramide and the role of IV metoclopramide are emphasized.

Antineoplastic Agents↗
PubMed1982

The effect of enzyme therapy on plasma lipid levels in the elderly.

(1) An enzyme preparation, Vasolastine, administered intramuscularly, to a group of elderly subjects (mean age 81.7) reduced fasting plasma cholesterol and triglyceride levels by amounts which were proportional to their initial concentration. (2) Triglyceride levels 3 h after a fat-rich meal were also directly dependent on the initial fasting level. This relationship is lowered significantly after 25 days of Vasolastine treatment. (3) It is suggested that these observations, taken in conjunction with the results of in vitro studies, confirm that Vasolastine acts synergistically with endogenous lipoprotein lipase.

Aged↗
PubMed1982

Ethionine causes the formation of NG-monoethylarginine in nuclear proteins from regenerating rat liver.

In a previous report, administration of [3H]ethylethionine to partially hepatectomized rats was shown to ethylate two classes of proteins extracted from rat liver nuclei in 0.25 N HCl. Upon acid hydrolysis of the proteins, ethyl derivatives of both lysine and arginine were found. The arginine derivative which represented the major ethylated product is identified in this report as NG-monoethylarginine by the use of alkali hydrolysis. Administration of methionine along with the ethionine partially inhibited the ethylation. This suggests that the ethylation may proceed in a similar manner to normal protein methylation by which the methylases utilize S-adenosylmethionine as the ethyl donor. Using in vitro assays for both protein-lysine and protein-arginine methyltransferase it was found that only the protein-arginine methyltransferase could use radiolabeled S-adenosylmethionine as a substrate. The major product formed in this assay was identified as NG-monoethylarginine.

Animals↗
PubMed1982

Ethionine inhibits in vivo methylation of nuclear proteins.

Nuclear protein methylation was studied in regenerating rat liver by giving [methyl-3H]methionine 45 h after partial hepatectomy. Ethionine, a liver carcinogen, has been shown to alter the methylation patterns in a basic protein (histone) fraction, as well as an acidic protein (non-histone) fraction present in a 0.25 N HCl nuclear extraction. The proteins present in the 0.25 N HCl extraction were separated by chromatography using a Bio-Rex 70 cation exchange column. Polyacrylamide gel electrophoresis and total amino acid analysis showed the first protein fraction contained acidic large molecular weight non-histone proteins, while the second fraction contained basic small molecular weight histone proteins. Both fractions were then hydrolyzed, and the amino acids chromatographed on an Aminex A-5 cation exchange column. The histones were found to contain epsilon-N-mono, di and trimethyllysine derivatives; whereas the non-histone fraction contained these lysine derivatives and additional basic amino acid identified as NG,NG-dimethylarginine. Ethionine (0.5 mg/g body weight) was found to inhibit in vivo methylation of lysine to form epsilon-N-mono, di and trimethyllysine, 46, 52 and 68%, respectively. The formation of NG,NG-dimethylarginine was inhibited by 85%. Ethylation of these proteins was also studied by giving [ethyl-3H]ethionine. After hydrolysis, the non-histones were found to contain a labeled lysine and arginine derivative, but in the histone fraction only labeled lysine was found.

Animals↗
PubMed1982

A differential catecholamine response during prolonged exercise and passive heating.

Plasma catecholamines (Ca) increase over time during prolonged exercise at a constant work rate. Possible reasons for this include hypoglycemia, dehydration, increased perceived exertion, and rising body temperature. In an effort to ascertain the contribution of elevated core temperature on the plasma Ca response to prolonged exercise four trained men were studied under two thermal conditions during 45 min of bicycle exercise (approximately 60% Vo2max) and during passive heating. On one testing day each subject was heat-stressed during exercise wearing a nylon pullover shell and cotton pants, (heat stress treatment); on the second day fans were directed on the subjects exercising in a thermoneutral environment (fan treatment). The passive heating experiment was conducted in a hot water bath (41 degrees C). The exercise heat stress treatment produced a higher plasma norepinephrine (NE) concentration (P less than 0.05) in all subjects than the fan treatment. The plasma epinephrine (E) concentration was not significantly (P greater than 0.05) different during exercise in the heat stress treatment from that found during fan treatment. A rise in rectal temperature (Tre) during passive heating resulted in quantitatively small changes in plasma E and NE. The heat load combined with the exercise task produced an increase in plasma NE concentration greater than the sum of the values measured during exercise in the thermoneutral environment and passive heating. This suggested that the combination of stressors caused an augmentation of the sympathetic nervous system's response. Finally, the added heat load caused changes in plasma NE and little change in plasma E, suggesting a differential Ca response with heat stress.

Adult↗