Radiation resistance and thermal resistance vary as a function of culture temperature in logarithmically growing Saccharomyces cerevisiae and are related to the optimum temperature for growth. ...Radiation resistance and thermal resistance were also induced when cells grown at low temperatures were subjected to a heat shock at or above the optimum growth temperature. Exposure to ionizing radiation followed by a short incubation at low temperature also induced resistance to killing by heat. Heat-shocked cells are induced to a level of thermal and radioresistance much greater than the characteristic resistance level of cells grown continuously at the shock temperature. This high level of resistance, which resembles that of stationary-phase cells, decays to the characteristic log-phase level within one doubling of cell number after the heat shock. Both induction of resistance and decay of that induction require protein synthesis. It is postulated that induction of resistance by heat shock or ionizing radiation is a response of the cells to stress and represents a preparation to enter stationary phase.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In the past few years patients having severe head trauma have survived in growing numbers, and it is likely that they will be more frequently seen on rehabilitation units. They display, in addition ...to direct structural damage, medical and neurologic problems which may be encountered during their rehabilitative phase. The purpose of this study will be to identify those medical and neurologic problems of consequence and describe their frequency of occurrence within a population of head injured patients. A consecutive series of 180 patients with head trauma undergoing rehabilitation were therefore reviewed, and the type and frequency of medical problems were noted. Neurologic, gastrointestinal, genitourinary, respiratory, cardiovascular, skin, musculoskeletal, and endocrinologic problems were encountered most frequently. Of these, ventricular dilatation, posttraumatic seizures, abnormal liver function tests, hypertension, thrombophlebitis, respiratory infections, periarticular heterotopic ossification, and pituitary-hypothalamic dysfunction are discussed in terms of their morbidity, clinical significance, and therapeutic approach. In many instances, these problems were not identified in the acute care hospital. Awareness of these potential conditions during the rehabilitation period can result in early detection and treatment.
We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here ...that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of^{90}{\rm Sr}/{}^{90}{\rm Y}$β radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and >80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment (44°C, 30 min) along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of β radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability. Radiation exposure resulted in a decrease in the risk of an MNNG initiation event which led only to the third type of cell. The data therefore indicate that the risk of some, but not all, tumor-initiating events caused by alkylating agents can be reduced by an exposure to ionizing radiation.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
As part of a study of the association between changes in mood and migraine attacks, daily self-report data on anxiety and depression were collected from 37 female patients attending a migraine ...clinic. A combination of the Irritability Depression Anxiety (IDA) Scale and two visual analogue scales (VAS) was used. The IDA and VAS measures of anxiety and depression were significantly associated in only 55 and 61 per cent of patients respectively.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The action of hyperthermia treatments on tumor promotion separated into a two-stage protocol has been investigated. 7,12-Dimethylbenzaanthracene (DMBA) initiated dorsal skin of female SENCAR mice was ...promoted with either H2O2 or 12-O-tetradecanoylphorbol-13-acetate (TPA) (4 applications, 2 times/week) as the first stage of promotion, followed by promotion with mezerein (28 applications, 2 times/week) as the second stage. Hyperthermia (44 degrees C, 30 min) treatment of the skin at the time of stage II promotion only (just before each mezerein application) suppressed 100% of papillomas when H2O2 was used as a first-stage promoter and 96% when TPA was used as the first stage, as compared to unheated control animals. The same hyperthermia treatment given only at stage I of promotion had similar results. Hyperthermia treatments just before stage I TPA promotion (4 treatments only) followed by mezerein as the second stage reduced papilloma formation by 92%. When H2O2 was used as the first stage promoter and again mezerein as the second, papilloma frequency was reduced by 74%, as compared to unheated controls. This antipromotion activity of hyperthermia could not be linked to an inhibition of skin protease activity. Although papilloma frequency was markedly suppressed by hyperthermia during stage I promotion only, carcinoma formation was not. A similar number of carcinomas appeared in the groups of mice receiving hyperthermia with either H2O2 or TPA as first-stage promoters, as in comparable groups receiving no hyperthermia. In contrast, when hyperthermia treatments were given during stage II promotion with mezerein (using either H2O2 or TPA as stage I promoters), carcinomas (as well as papillomas) were markedly reduced. The results suggest that DMBA initiation creates two types of promotion-dependent cells, a majority with relatively low progression probability and a minority with relatively high progression probability. The former require both stage I and II promotion while the latter require only stage II promotion to form tumors. Hyperthermia treatments given during stage II promotion protected against promotion and progression of both types of initiated cells, but similar treatments only during stage I did not protect against promotion and progression of the latter. Although promotion was required for expression, relative progression probability appeared linked to initiation and not promotion events. These findings suggest that hyperthermia treatment of persons exposed to tumor-promoting agents may reduce the risk of induced tumorigenesis.
We have shown previously that a heat shock induces a transient increase in the resistance of wild-type Saccharomyces cerevisiae to the lethal effects of ionizing radiation. This increase was similar ...to the increase in resistance to thermal killing induced by the same heat shock, but appeared at a slightly earlier time after the temperature increase. We now show that while excision-defective mutants respond like the wild type, recombination-deficient mutants do not display this heat-shock induction of radiation resistance, but still show induction of thermal resistance. The maximum ability for recombinational repair after a heat shock was measured directly (by gene conversion) in wild-type diploids and was found to increase transiently with kinetics very similar to the increase in resistance to the lethal effects of a single dose of radiation. Radiation survival curves of wild-type cells exposed to the elevated temperature were able to resolve two populations of cells on the basis of their sensitivity to ionizing radiation. Following a heat shock, the proportion of resistant cells increased temporarily in parallel with the increase in radiation resistance. We conclude that heat-shock induction of radiation resistance in wild-type diploid yeast results from at least two changes, an increase in recombinational repair capacity, possibly associated with Gl cells, and a shift in population distribution to a higher fraction of resistant cells. We further conclude that heat-shock induction of thermal resistance proceeds by an independent mechanism.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
When exponentially growing diploid wild type Saccharomyces cervisiae cells were subjected to a sudden rise in temperature (heat shock) they responded by increasing their resistance to the lethal ...effects of ultraviolet light. We have previously reported heat shock-induced increases in heat and ionizing radiation resistance. The shock-induced rise in resistance to uv light reported here was examined in terms of DNA repair capacity, and we find that the increase is due to induction of the recombinational repair system with no significant response from the uv-excision repair process.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A single hyperthermia treatment given near the time of initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenzaanthracene (DMBA) increased the number of initiated cells in ...the skin of SENCAR mice subjected to a two-stage tumorigenesis protocol. In animals subsequently promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA), a 44 degrees C, 30-min hyperthermia treatment given just before, just after or 24 h before MNNG initiation increased the average papilloma frequency by 40-50%. In the groups of animals that received a hyperthermia treatment just before MNNG initiation, tumor latency was reduced by 40-60%. Treatment with MNNG in the absence of hyperthermia produced two classes of initiated cells. One type, formed in low yield, was independent of TPA promotion and formed tumors with a high probability of progression to malignancy. The other type was promotion dependent, and formed in relatively high yield but produced tumors with a probability of progression to carcinomas approximately 10-fold less than promotion-independent initiated cells. A single hyperthermia treatment given just before or just after MNNG initiation increased the yield of both promotion-dependent and promotion-independent initiated cells, and consequently increased the yield of carcinomas. In animals given a single hyperthermia treatment 24 h prior to initiation (to induce thermotolerant skin cells), MNNG exposure resulted in an increased yield of promotion-dependent initiated cells but no change in the yield of promotion-independent initiated cells. Hyperthermia treatment of DMBA-initiated skin increased the yield of initiated cells (promotion-dependent) only when given just after exposure to the initiator. The extra initiated cells produced by hyperthermia treatment of MNNG or DMBA exposed skin had the same probability of progression to carcinomas as initiated cells produced by the same initiation in the absence of hyperthermia. As noted previously for DMBA-initiated mice, hyperthermia given at the time of each application of TPA promoter also suppressed the formation of papillomas initiated by MNNG. Only the promotion and progression of promotion-dependent initiated cells, and not of promotion-independent cells, was suppressed. The results show that a single hyperthermia treatment near the time of exposure to an alkylating agent increased the number of both promotion-dependent and promotion-independent initiated cells and, as a consequence, increased the risk of carcinogenesis associated with that exposure.
Human genotypes are known "that confer both increased susceptibility or resistance to DNA damage and increased cancer risk after exposure to carcinogenic agents, including ionizing radiation" (NAS ...1980). The existence of sensitive subgroups at elevated risk, if they are of appreciable size, could have significant impact on the actual distribution of risk. The radiosensitive disorder ataxia-telangiectasia (A-T) serves as a good example: the significant "at risk" group, A-T heterozygotes, is estimated to comprise between 0.5% and 5% of the total population, and has a twofold elevated lifetime risk of fatal neoplasia. Other genetic syndromes that manifest abnormal radiosensitivity are also known, but no estimates are available for the population frequency of all such phenotypes, or for their overall degree of increased risk. As the first part of a program addressing these questions, we have developed a rapid and inexpensive assay for screening members of the general population for abnormal radiosensitivity; such persons would be regarded as at presumptive elevated risk of radiogenic cancer. Our method utilizes lymphoblastoid cell lines and chronic as opposed to acute gamma-ray exposure to amplify the difference between normal and somewhat sensitive strains. A simple "grow-back" assay assesses the survival response. Information on the extent of natural variation in inherited susceptibility to radiogenic cancers could be most useful for radiation protection in the future.
In a two-stage skin tumorigenesis protocol 7,12-dimethylbenzaanthracene (DMBA) initiation followed by twice weekly 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion, SENCAR mice developed an ...average of approximately 8.5 papillomas per animal. Hyperthermia treatments of the initiated skin (44 degrees C, 30 min) immediately before or after each TPA application (for 90 days) reduced papilloma frequency 80-90%. Animals whose initiated skin was made thermo-tolerant at the time of TPA application (by hyperthermia treatment 24 h prior to each application of promoter) showed slightly less protection (approximately 70% reduction in frequency). Multiple 44 degrees C hyperthermia treatments alone (27 X, twice a week) had no promoting activity in DMBA-initiated skin. The usual responses of skin to TPA promotion, including an increase in dark cells, epidermal thickening, reddening and erosion were all suppressed in animals treated with hyperthermia near the time of TPA application. The effect of hyperthermia on tumorigenesis was at the promotion stage and the survival of initiated cells was not affected, since the normal number of papillomas was produced when TPA promotion was delayed until after the multiple (27 X, twice a week) hyperthermia treatments were completed. Hyperthermia treatments (44 degrees C, 30 min, twice weekly for 90 days) given near the time of TPA application also suppressed the incidence of carcinomas appearing within 300 days. About 40% of the DMBA-initiated, TPA-promoted animals developed a carcinoma, compared with only approximately 10% of a similar group which received hyperthermia treatments near each TPA application. Papillomas appearing in spite of hyperthermia treatments during promotion were not more likely to progress into carcinomas than those appearing in unheated animals. Such hyperthermia treatments given to animals bearing pre-existing papillomas did not markedly alter the subsequent development of carcinomas compared with unheated controls. The results demonstrated that 44 degrees C hyperthermia applied near the time of TPA promotion acted as a powerful antipromoter and suppressed the appearance of both papillomas and carcinomas, apparently by acting at an early stage of promotion.
