Ventilatory and metabolic reactions to heat stress during prolonged exercise.
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Biomedical subjects
Publications and source records attributed to R Cox.
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A study of home monitoring of blood glucose in diabetic pregnancy was made by a retrospective analysis of medical records of women who attended Christchurch Women's Hospital from 1976 to 1980. Of 20 previously-diagnosed insulin-dependent diabetics eight had used home blood glucose meters during pregnancy. The meter users spent on average 23.9 fewer days in hospital and attended on average 4.2 more antenatal clinics. Otherwise management and outcome were equivalent. We conclude that home monitoring of blood glucose is an effective and safe means of minimising hositalisation in diabetic pregnancy without compromising outcome.
Nicotinamide is methylated via S-adenosylmethionine (AdoMet) and excreted in the urine as N1-methylnicotinamide. Since S-adenosylethionine (AdoEth) inhibits nicotinamide methyltransferase, ethionine (0.75 mg/g body wt) was given to rats and its effect on the urinary excretion of N1-methylnicotinamide was examined. Nicotinamide (0.5 mg/g body wt) gave a 13.6-fold increase in the 24-h urine concentration of N1-methylnicotinamide. However, ethionine given 4 h prior to nicotinamide completely prevented this increase by nicotinamide. It appears at ethionine via AdoEth inhibits nicotinamide methyltransferase in vivo and lowers the urine level of N1-methylnicotinamide.
The repair of potentially lethal damage (PLD) after X-rays was studied in plateau phase cultures of nine normal and five ataxia telangiectasia (AT) strains of human fibroblasts. In the normal strains PLD repair was complete after 6 hours of post-irradiation incubation. There were differences in the form of the survival curves of normal strains after maximum PLD repair but the extent of post-irradiation recovery was similar in all strains. In contrast all AT strains were almost completely deficient in PLD repair even when post-irradiation incubation was extended to 18 or 24 hours. The relevance of the PLD repair-deficiency in cultured AT strains to in vivo radiotherapeutic observations in AT patients is briefly discussed.
This paper tests whether photon absorption processes in particular atomic element(s) may be responsible for the observed high relative biological effectiveness (RBE) of ultrasoft X-rays. The effectiveness of titanium K characteristic X-rays (4.55 keV) is compared with previous observations for aluminium (1.5 keV) and carbon (0.28 keV) K ultrasoft X-rays. For a given absorbed dose, five times more Ti K than Al K photons are absorbed in phosphorus; since Al K X-rays are observed to be more effective in killing human and hamster cells it is concluded that absorption in phosphorus does not play a dominant lethal role. This is supported by the observation that the absolute number of Al K photons absorbed in phosphorus of DNA of human fibroblasts is less than 1 per lethal event. For no element is the relative number of absorbed photons of the three X-ray energies even approximately proportional to their observed RBEs. The effectiveness of ultrasoft X-rays is apparently not due to selective absorption but rather to the secondary electrons; consequently the mechanism of action should be common to the large numbers of low energy secondary electrons produced by most other ionising radiations, including gamma-rays.
The possible role of alterations of histone methylation by ethionine in the mechanism of ethionine carcinogenesis was studied. In regenerating rat liver, histone synthesis was inhibited by only 20 to 30% with large doses of ethionine (0.75 to 1.0 mg/g body weight). The effect of ethionine on the in vivo methylation of histones was studied by giving 0.5 mg ethionine and [methyl-3H]methionine per g body weight. In vivo methylation of lysine was inhibited by 50%, whereas the arginine methylation was inhibited by 89%. The cellular localization of the methyltransferases and S-adenosyl-L-ethionine may be related to this differential effect. Utilizing an in vitro assay for protein-lysine and protein-arginine methyltransferases, we have demonstrated that the methyl-deficient histones are transported to the nucleus and with time lose their ability to accept methyl groups in vitro.
The management of all patients with abdominal aortic aneurysms attending a district general hospital over a 6-year period is reviewed. The hazards of delaying surgical treatment are emphasised. An operative mortality of 12% for non-leaking and 55.6% for leaking aneurysms is discussed with reference to other published results. Attention is drawn to the relatively high proportion of patients not undergoing surgical treatment. Some ways in which the mortality of the condition might be reduced are considered.
A retrospective assessment of the daily blood glucose measurements over a period of four weeks was carried out on 38 insulin-dependent diabetics. It was found that for five pregnant diabetics and three diabetics with poor control, mean blood glucose fell from 9.6 to 7.9 and 14.4 to 11.0 mmol/l respectively. In contrast to eight overseas reports on home monitoring, the remaining patients made no significant improvement in their mean blood glucose at the end of four weeks. We conclude that this is probably due to the minimal supervision and possibly to the relatively short period of self-study by these patients. However, 50 percent reported fewer episodes of hypoglycaemia and 89 percent wished to continue blood testing.
A biophysical analysis is made of the results of recent experiments which used accelerated heavy ions of 20 to 470 keV micron-1 to induce inactivation and mutation (resistance to 6-thioguanine) in cultured V79 Chinese hamster cells and HF19 human diploid fibroblasts. It is shown that the discrete nature of the primary ions must be explicity taken into account before the numbers of induced lethal and mutagenic lesions can be deduced from the observed radiosensitivities. The measured numbers of lesions produced by the radiations of different LET are compared with the relative numbers predicted by various models of radiation action. The observations can be explained on the hypothesis that each lethal lesion is produced by a deposition of small energy (small number of ionizations) in a distance of about 3 nm. Two different lesions appear to be involved, one of which requires greater than or equal to 100 eV and is dominant with low-LET radiations, and the other requires greater than or equal to 300 eV and is dominant at high-LET. Similar conclusions may apply to mutagenic lesions except that the mechanism which dominates at high-LET requires significantly more than 300 eV. More precise assessments of the hypothesis and these numerical values must await detailed track structure calculations of the radiation on the nanometre scale. Alternative models which invoke 'accumulation of sublethal damage' or 'interaction between sublesions', over distances of the order of microns, do not provide a consistent explanation of the observations. This suggests that the frequently observed curvature of low-LET dose-responses is not due to interaction between sublesions but rather to some other mechanism such as a dose-dependent repair process. It is also shown that low velocity, high-LET ions produce an average of appreciably less than one lethal lesion in traversing the nucleus of the above mammalian cells; 90 keV micron-1 helium ions produce about 0.03-0.06 lethal lesions micron-1 of track through the nucleus of the cells of thickness about 7 microns. Some estimates are also made of the size of the nuclear region which is sensitive to the induction of mutation to 6-thioguanine-resistance; it is concluded that this region extends beyond the DNA of the structural gene itself.
Induction of structural chromosome aberrations was studied in human peripheral blood lymphocytes irradiated in the unstimulated state with ultrasoft X-rays. Aluminium K X-rays (1.49 ke V) and carbon K X-rays (0.28 ke V) were used. The frequencies of dicentric aberrations and of excess acentric fragments were found to increase approximately linearly with absorbed dose of both radiations. Carbon X-rays were more effective than aluminium X-rays. The corresponding linear yield coefficients for dicentrics are (3.7 X 10(-1)) Gy-1 and (2.2 X 10(-1)) Gy-1 respectively. AT low doses both these radiations are more effective than hard X-rays in producing dicentric aberrations, but at high doses aluminium X-rays are less effective than hard X-rays because of the large positive curvature of the hard X-ray dose-response. The most significant observation of these experiments is that electrons of less than 280 eV, produced by carbon X-rays, are efficient in producing dicentric aberrations. This implies that single local energy events of about 14 ionizations with in less than 7 nm are able to produce exchange aberrations.
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During the last 2 decades, the introduction of new isotopes for both removable (192Ir) and permanent (125I) interstitial implants, along with the availability of computerized dosimetry and the refinement of implantation techniques have all contributed to a Renaissance of brachytherapy. Techniques of implantation and the results of such procedures at the Stanford Medical Center for the 3 most commonly implanted carcinomas (breast, prostate, head and neck) are all presented in detail. Other anatomic sites which may be treated by interstitial irradiation are also described.
Several alkylating carcinogens were tested for their ability to inhibit DNA methylation in an in vitro assay. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was the only carcinogen studied that altered the methylase activity. It was further demonstrated that MNNG reacts with the DNA methylase protein and produces a mixed type of inhibition. Prevention of the MNNG effect by dithiothreitol and inhibition of the DNA methylase with iodoacetamide suggest that DNA methylase is a sulfhydryl-containing enzyme and that MNNG inactivates the enzyme by reacting with sulfhydryl groups.
The abuse of phencyclidine [1(1-phencylohexyl)piperidine, PCP], commonly referred to as angel dust or hog, is rapidly reaching epidemic proportions. PCP users often appear violent and increases in PCP-implicated homicides and suicides have been reported. In animal studies PCP has been demonstrated in brain up to 48 h after administration, long after blood levels become undetectable. However, there is little further information on the distribution of PCP within the central nervous system with regard to the possible sites of action. Recently, Sokoloff and associates described a new technique which can be used to visualise possible sites of drug action. The technique is based on the premise that neuronal activity is closely related to energy metabolism. Therefore, by directly monitoring 2-deoxy-D-glucose consumption before and after a pharmacological stimulus, we can obtain autoradiographic evidence of changes in neuronal activity in discrete areas brain as a response to that stimulus. Using this procedure, we now report that PCP causes dramatic changes in glucose metabolism in very specific regions of the rat brain.
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Stimulation of postconfluent Swiss 3T3 cells in serum-free medium with 4.3 mM Ca2+ results in marked increases in both released and cell-associated plasminogen activator (PA). Increased release of PA commenced approximately 10 to 12 hours post-stimulation and continued to increase steadily until 48 hours at which time the stimulates cells (4.3 mM Ca2+) released approximately 14 times more PA than control cells (1.8 mM Ca2+). Sr2+, like Ca2+, also stimulates PA synthesis/release either in the presence or in the absence of 1.8 mM Ca2+ whereas an excess of Mg2+ inhibits Ca2+ stimulation. Supranormal [Pi] in the medium stimulates PA synthesis/release in the presence of 1.8 mM mM Ca2+. Further, optimal stimulation by 4.3 mM Ca2+ requires a normal level of Pi (1.0 mM). Elevation of medium [Ca2+] or [Pi] results in an enhanced uptake of Ca2+. The facts that cycloheximide treatment completely abolishes the Ca2+ stimulatory effect and that an increase in cell associated PA precedes release indicate that PA release is coupled to synthesis of new PA. Ca2+ stimulation of PA synthesis/release also requires continuous energy production and RNA as well as protein synthesis. A hypothesis is proposed to explain the relationship between stimulation of PA production and its enhanced release from cells stimulated by elevated [Ca2+] or [Pi] in the media. The possibility that PA release may be an example of the phenomenon of membrane shedding as opposed to secretion is discussed.
N-methyl-N-nitrosourea (MNU) was instilled by a urethral catheter into the urinary bladders of female Wistar rats in weekly doses of 0.5 mg for 1, 2, 3 and 4 weeks. At 75 weeks after the initial dose of MNU, the incidences of bladder cancer were 0, 7, 50 and 64% for the total doses of MNU of 0.5, 1.0, 1.5 and 2.0 mg, respectively. Control rats instilled with 0.9% NaCl only for 1--4 weeks did not develop bladder cancer by 75 weeks. Higher doses of MNU of 4.0 and 6.0 mg, given weekly in 0.5 mg amounts for 8 and 12 weeks, respectively, induced a higher incidence (nearly 90%) of urinary bladder cancer in rats at 22--28 weeks. However, it was shown that control rats given 12 weekly installations of solvent only developed a significant number (33%) of bladder cancers by 22--28 weeks.