Biomedical subjects

D P Morrison

Publications and source records attributed to D P Morrison.

At least 37 records · Page 2Linked to original sources

PubMed1989

The prevalence of psychiatric disorder among female new referrals to a migraine clinic.

In a consecutive series of 46 female new referrals to a migraine clinic, 17 patients (37%) complained of increased irritability and/or depression in association with more than 50% of their migraine attacks. This was not related to the attack frequency or duration. Sixteen patients (33%) met DSM-III criteria for a current diagnosis of an affective syndrome and when present this was significantly associated with these complaints.

Adult↗

PubMed1988

The influence of a hyperthermia treatment on chemically induced tumor initiation and progression in mouse skin.

A single hyperthermia treatment given near the time of initiation with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz[a]anthracene (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.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1988

Impact on radiogenic cancer risk of persons exhibiting abnormal sensitivity to ionizing radiation.

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.

Cell Line↗

PubMed1987

Inducible DNA-repair systems in yeast: competition for lesions.

DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate that in this lower eukaryote, mutagen exposure does not necessarily result in a fixed risk of mutation, but that the risk can be markedly influenced by a variety of external stimuli including heat shock or exposure to other mutagens.

DNA Damage↗

PubMed1987

Tumorigenesis and carcinogenesis in mouse skin treated with hyperthermia during stage I or stage II of tumor promotion.

The action of hyperthermia treatments on tumor promotion separated into a two-stage protocol has been investigated. 7,12-Dimethylbenz[a]anthracene (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.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1986

Effects of oral physostigmine and lecithin on memory and attention in closed head-injured patients.

In view of the evidence for the role of the central cholinergic pathways in memory and preliminary studies suggesting alteration of neurotransmitters after severe head injury, we completed a double-blind, placebo-controlled study of combined oral physostigmine and lecithin. Sixteen survivors of moderate to severe closed head injury who had unequivocal memory deficit were studied during the course of inpatient rehabilitation. Although the results generally indicated no difference in the effects of the physostigmine-lecithin combination as compared to lecithin alone, sustained attention on the continuous performance test was more efficient under physostigmine than placebo when the drug condition occurred first in the crossover design. Further investigation of neurotransmitter manipulation is warranted in patients with traumatic brain injury.

Administration, Oral↗

PubMed1986

Measurement of enzyme activities in mouse epidermis following phorbol ester treatment: a potential artifact.

After application of tetradecanoylphorbol acetate to mouse skin, a decrease in the specific activity of catalase in epidermal extracts has been observed, confirming the observation of earlier workers. However, this decrease in specific activity is largely due to an increase in extractable protein and not an actual decrease in catalase activity per animal skin. Thus changes in specific activity of components in epidermal extracts need to be interpreted with caution.

Animals↗

PubMed1986

Hyperthermia and phorbol ester tumor promotion in mouse skin.

In a two-stage skin tumorigenesis protocol [7,12-dimethylbenz[a]anthracene (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.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1985

The impact of lithium in South-west Scotland. I. Demographic and clinical findings.

A point-prevalence study in South-west Scotland found that 0.77 per 1,000 of the total population were receiving lithium. Almost one quarter had done so for more than ten years. At the time of lithium commencement, only 68% had always been diagnosed as having an affective illness; 59% of the patients were also receiving antidepressants, major tranquillisers, or both. Though this might be due in part to unnecessary administration of supplementary drugs, 19% of non-inpatients had moderate depressive symptoms, significant depressive illness, or manic symptoms. Lithium side-effects were prominent: 30% of the sample complained of weight gain, thirst or excessive micturition; 42% had noticed hair changes; and 7% had diminished thyroid activity, but most patients believed they had benefited considerably from lithium therapy.

Adolescent↗

PubMed1985

The impact of lithium in South-west Scotland. II. A longitudinal study.

In a longitudinal study in South-west Scotland of patients suffering mainly from affective illness, the introduction of lithium as prophylactic therapy was associated with a significant reduction in the number and length of hospital in-patient admissions, as well as in the number of courses and total number of electro-convulsive treatments. However, there was no significant reduction in the length of time patients received either antidepressants or major tranquillisers. A rating of individual patients suggested that a bare majority (52%) had improved considerably following the introduction of lithium.

Adolescent↗

PubMed1985

The impact of lithium in South-West Scotland. III. The discontinuation of lithium.

A review in South-West Scotland of all patients prescribed lithium for the first time during the years 1972-82 showed that on average, 12 per 100,000 of the general population start this drug each year. By the end of the period, lithium had been stopped in 58% of patients; the most common reason for discontinuation was the development of side-effects, of which tremor was the most frequent. In only 15% was lithium stopped as it was considered no longer necessary; 44% of patients discontinued lithium within one year of starting it.

Adult↗

PubMed1985

Medical problems encountered during rehabilitation of patients with head injury.

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.

Adolescent↗

PubMed1984

Is DNA damage the signal for induction of thermal resistance? induction by radiation in yeast.

Yeast, as well as higher eukaryotes, are induced to increase thermal resistance (thermotolerance) by prior exposure to a heat stress. Prior exposure to an acute dose of either 60Co gamma or 254-nm ultraviolet radiation, at sublethal or fractionally lethal doses, is shown to cause a marked increase in the resistance of Saccharomyces cerevisiae to killing by heat. Following a radiation exposure, thermal resistance increased with time during incubation in nutrient medium, and the degree of resistance reached was proportional to the dose received. Partial induction by radiation followed by maximum induction by heat did not produce an additive response when compared to a maximum induction by heat alone, suggesting that the same process was induced by both heat and radiation. Irradiation with 254-nm uv light followed by an immediate, partial photoreversal of the pyrimidine dimers with long-wavelength uv light resulted in a reduced level of resistance compared to cells not exposed to the photoreversal light, indicating that the cells specifically recognized pyrimidine dimers as a signal to increase their thermal resistance. Exposure to 254-nm uv or ionizing radiation induced thermal resistance in mutants defective in either excision repair (rad3, uv-sensitive) or recombinational repair (rad52, gamma-sensitive), suggesting that recognition and repair of DNA damage by these systems are not a part of the signal which initiates an increase in resistance to heat. The amount of induction, per unit dose, was greater in the DNA repair-deficient mutants than in the wild-type cells, suggesting that an increase in the length of time during which damage remains in the DNA results in an increase in the effectiveness of the induction. These data indicate that types of DNA damage as diverse as those produced by ionizing radiation and by ultraviolet light are recognized as a signal by the yeast cell to increase its thermal resistance. It is therefore suggested that heat-induced alterations in DNA or in DNA-dependent chromosomal organization may be the signal for heat induction of thermotolerance in this and other eukaryotes.

Acclimatization↗

PubMed1984

An oxygen effect for gamma-radiation induction of radiation resistance in yeast.

Previous evidence in a lower eukaryote indicated the lack of an oxygen effect for ionizing radiation induction of radioresistance [P. E. Bryant, Nature (London) 261, 588-590 (1976)], suggesting that the signal for induction may be different from that in prokaryotes, where DNA damage by a variety of agents has been shown to induce SOS. type repair and radioresistance. We show here that prior exposure to a sublethal dose of gamma radiation caused induction of radioresistance in Saccharomyces cerevisiae, and that the rate of induction was proportional to the initial dose. Irradiation in oxygen produced a higher rate of increase in resistance, per unit dose, than irradiation in nitrogen, with an oxygen enhancement ratio of 2.8. The maximum level of resistance reached in response to saturating doses was the same regardless of the presence or absence of O2 during the initial irradiation. At less than saturating doses, however, the maximum increase in resistance was higher, per unit dose, following irradiation in the presence of O2 than in its absence. Oxic doses which gave the maximum possible in increase the level of resistance were considerably less than those required to produce the maximum rate of increase in resistance. These results suggest a difference in the level at which DNA damage saturates these processes. These results also indicate that the use of DNA damage as a signal for induction of radiation resistance has probably been conserved during the evolution of prokaryotes to lower eukaryotes.

Cell Survival↗

PubMed1983

The Crichton Visual Analogue Scale for the assessment of behaviour in the elderly.

A visual analogue scale has been constructed to allow relatives and professionals to rate the behaviour of elderly patients. The scale has been shown to have good inter-rater reliability, test-retest reliability and validity. It is suggested that the scale can provide a quick and convenient initial assessment of the patient either at home or in hospital, and possibly also a measure of change.

Activities of Daily Living↗

PubMed1983

Assessment of the role of oxygen and mitochondria in heat shock induction of radiation and thermal resistance in Saccharomyces cerevisiae.

In response to a heat shock, the yeast Saccharomyces cerevisiae undergoes a large increase in its resistance to heat and, by the induction of its recombinational DNA repair capacity, a corresponding increase in resistance to radiation. Yeast which lack mitochondrial DNA, mitochondria-controlled protein synthetic apparatus, aerobic respiration, and electron transport rho 0 strain) were used to assess the role of O2, mitochondria, and oxidative processes controlled by mitochondria in the induction of these resistances. We have found that rho 0 yeast grown and heat shocked in either the presence or absence of O2 are capable of developing both radiation and heat resistance. We conclude that neither the stress signal nor its cellular consequences of induced heat and radiation resistance are directly dependent on O2, mitochondrial DNA, or mitochondria-controlled protein synthetic or oxidative processes.

DNA, Fungal↗

PubMed1983

Heat-shock induction of ultraviolet light resistance in Saccharomyces cerevisiae.

When exponentially growing diploid wild type Saccharomyces cerevisiae 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.

Diploidy↗

PubMed1983

A comparison between rates of cell death and DNA damage during irradiation of Saccharomyces cerevisiae in N2 and N2O.

Yeast and several other organisms are more sensitive to the lethal effects of ionizing irradiation if exposed in the presence of N2O as compared to N2. It has been suggested that this increased sensitivity is due to the cooperative effects of OH and H2O2 generated external to the cell wall. Using diploid yeast, wild type for radiation resistance, we have compared the rates of cell death due to gamma irradiation in N2 and N2O with the rates of DNA damage measured by gene conversion of trp- to trp+ (a recombinational repair event). We find that DNA damage as measured by gene conversion increases at a faster rate, per unit dose, during irradiation in N2O as compared to N2, just as lethality was higher in N2O. When DNA damage was compared in N2 and N2O at equal levels of survival, however, there was no significant difference between the two irradiation conditions. Therefore, increased lethality during irradiation in N2O seems to be directly due to increased DNA damage. If the observed increased lethality results from external OH and H2O2, the effect of these highly reactive species is expressed by increased internal damage at the level of DNA.

DNA Repair↗