Adenosine, blood pressure and NREM delta.
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Animals↗
Biomedical subjects
I G Campbell
Publications and source records attributed to I G Campbell.
Intra-individual variation of plasma lipids and lipoproteins in prepubescent children.
Estimates of the average intra-individual biological variability for plasma lipids and lipoproteins differs substantially among published studies. Moreover, this topic does not appear to have received consideration in exercise and health literature with normal, healthy children as subjects. The purpose of this study was, therefore, to determine the short-term, day-to-day variability of the lipid-lipoprotein profile from 19 children [mean (SD), 11.5 (0.8) years] from 3 separate venous blood samples. Intra-individual standard deviations, variances and coefficients of variance were determined for total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), HDL-C sub-fractions HDL2 and HDL3, and low-density lipoprotein-cholesterol (LDL-C). The intra-individual variation for TC and LDL-C was used to calculate the 95% confidence intervals (CIs) around the National Cholesterol Education Programme (NCEP 1991) cut-off points. The main finding was that all of the measured blood analytes including TC, TG, HDL-C, HDL2, HDL3, and LDL-C varied considerably from day-to-day. Coefficients of total variation ranged from 3.5% for HDL3 to 25.4% for TG. Classification of individuals using NCEP guidelines was difficult based on only one or two blood samples. The magnitude of variation for LDL-C meant that a 95% CI could not be constructed around the NCEP borderline-high classification from either one or two samples. However, averaging three TC and LDL-C measurements increased the likelihood of classification within the 95% CI. The results indicate that when using the NCEP guidelines for children and adolescents, true concentrations for TC and LDL-C should be based on the mean of multiple samples.
Aging↗
Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis.
Impaired galactose metabolism has been proposed as a risk factor for ovarian cancer and endometriosis, which is a putative precursor of endometrioid and clear cell histological sub-types of ovarian cancer. The prevalence of the most common galactose-I-phosphate uridyl transferase gene mutations, Q188R and N314D, was assessed in 206 women with ovarian cancer, 78 women with endometriosis and 248 controls. No Q188R mutations were found in any of the groups. A statistically significant increase in the frequency of N314D mutations was observed in women with serous and undifferentiated histological sub-types of ovarian cancer, but not mucinous, endometrioid or clear cell sub-types. There were no significant differences observed in the N314D mutation frequency between women with endometriosis (18%) and controls (17%). Our results support previous reports of an association of impaired galactose metabolism with serous and undifferentiated ovarian cancers but contradict previous findings of increased N314D mutation frequencies among women with endometriosis and endometrioid and clear cell sub-types ovarian cancer.
Adult↗
Loss of heterozygosity on chromosomes 7p, 7q, 9p and 11q is an early event in ovarian tumorigenesis.
Forty early stage malignant and seven borderline ovarian tumours were analysed for loss of heterozygosity (LOH) on chromosomes 6, 7, 9, 11 and 17. LOH involving at least one locus was observed in 32 (80%) early stage and six (86%) borderline tumours. Frequent LOH in the early stage tumours was detected on chromosome arms 7p (31%), 7q (50%), 9p (42%) and 11q (34%) suggesting that these chromosomes harbour tumour suppressor genes which are inactivated early in tumorigenesis. Borderline tumours exhibited a similar pattern of LOH to that observed in the early stage malignant tumours, indicating that the development of both malignant and borderline forms may involve inactivation of the same set of tumour suppressor genes. Together with our previous investigation of benign ovarian tumours this data supports the theory that malignant ovarian tumours may arise from benign and borderline precursors.
Chromosomes, Human, Pair 11↗
Haloperidol potentiates the EEG slowing of MK-801 despite blocking its motor effects: implications for the PCP model of schizophrenia.
Haloperidol (HP) can block both the motor stimulation and the neurotoxic vacuolization of MK-801, suggesting that the two drugs have antagonistic brain actions. However, we show here that the modest EEG slowing produced by HP and MK-801 individually is massively potentiated when the drugs are combined. This finding challenges the argument for the PCP model of schizophrenia that assumes a general antagonism of neuroleptics and NMDA channel blockers. It further suggests that blockade of MK-801 motor effects is an inadequate test for antipsychotic drug actions. Our data indicate that intact function of D2 receptors (or other HP targets) is required to prevent generalized EEG slowing in the presence of NMDA channel blockade, a possibility of potential clinical interest.
Animals↗
Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors.
Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endometrial implants called endometriosis and not the ovarian surface epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor implicated in the pathogenesis of a wide variety of malignancies, but to date, somatic mutations in PTEN have not been identified in studies of predominantly serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in tumors of the endometrioid type but have rarely been found in serous types, and we hypothesized that a similar histological subtype bias might be occurring in ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29 serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on 10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the endometrioid (43%) and serous (28%) tumors but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the endometrioid tumors, and in all informative cases, the mutation was accompanied by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown to harbor two somatic PTEN mutations. In this tumor, the histological appearance of the mucinous areas was atypical, and the mucinous areas contained foci of endometrioid differentiation. The majority of tumors with PTEN mutations were grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in ovarian tumorigenesis. No PTEN mutations were found among the serous or clear cell tumors. The identification of frequent somatic PTEN mutations in endometrioid ovarian tumors indicates that it plays a significant role in the etiology of this subtype. The absence of mutations in other histological subtypes is consistent with the hypothesis that epithelial ovarian cancers arise through distinct developmental pathways.
Adenocarcinoma, Clear Cell↗
Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage.
Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.
Adult↗
TP53 intron 6 polymorphism and the risk of ovarian and breast cancer.
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Alleles↗
BRCA1 mutations in southern England.
If genetic testing for breast and ovarian cancer predisposition is to become available within a public health care system there needs to be a rational and cost-effective approach to mutation analysis. We have screened for BRCA1 mutations in 230 women with breast cancer, all from the Wessex region of southern England, in order to establish the parameters on which to base a cost-effective regional mutation analysis strategy. Truncating mutations were detected in 10/155 (6.5%) consecutive cases selected only for diagnosis under the age of 40 (nine of these ten women had a strong family history of breast or ovarian cancer), 3/61 (4.9%) bilateral-breast cancer cases (all three mutations occurring among women for whom the first cancer was diagnosed under 40 years) and 8/30 (26.6%) breast cancer cases presenting to the genetics clinic (for whom a strong family history of breast and/or ovarian cancer was present). Ten different mutations were detected in 17 families, but three of these accounted for 10/17 (59%) of the families. The cost of screening the population for mutations in the entire BRCA1 gene is unacceptably high. However, the cost of screening a carefully selected patient cohort is low, the risk of misinterpretation much less and the potential clinical benefits clearer.
Adult↗
Symmetry of the elbow kinematics during racing wheelchair propulsion.
The purpose of this study was to establish whether bilateral symmetry exists during wheelchair propulsion in the elbow movement pattern of trained wheelchair racers. Seven endurance-trained wheelchair racers volunteered to participate in the study. Each subject was recorded by two-dimensional video analysis while pushing on a single-roller wheelchair ergometer at 14 mph (6.58 ms-1) in their own racing wheelchair. The range of elbow flexion, elbow orientation and selected timing parameters including cycle time and time spent in contact with the handrim (propulsion phase) were obtained from both left and right sides. Wilcoxon Matched-Pairs Signed-Ranks tests determined the differences between the left and right sagittal plane images of wheelchair propulsion. Furthermore, the Bland-Altman method determined the agreement between the left and right sagittal plane images. The results indicated that the propulsion phase, elbow height and elbow angular displacement characteristics were not significantly different between right and left sides. The right elbow was higher than the left during the recovery phase, but the magnitude of this difference was only 0.03 m (N.S). Factors associated with chair design and the athlete's posture may have contributed to the small differences noted between left and right sides. In conclusion, the results appear to suggest that the assumption of bilateral symmetry of the elbow movement pattern during wheelchair propulsion is valid for the group. However, it is important to note that asymmetries exist in individuals and further research is warranted.
Adolescent↗
Exercise training induced alterations in prepubertal children's lipid-lipoprotein profile.
PURPOSE: This study examined the effect of exercise training on prepubertal children's (ET, N = 28) lipid-lipoprotein profile, relative to a maturity matched control group (CON, N = 20). METHODS: Training for ET involved stationary cycling for 30 min, 3 times.wk-1 for 12 wk, at 79.3 +/- 1.2% (mean +/- SD) peak heart rate (HR). Controls maintained their usual lifestyle pattern. Plasma concentrations of total triacylglycerol (TG), total cholesterol (TC), and high-density lipoprotein (HDL)-cholesterol (HDL-C) were determined pre- and postintervention. Low-density lipoprotein (LDL)- cholesterol (LDL-C) was subsequently estimated from these concentrations, and the ratios TC/HDL-C and LDL-C/HDL-C were also calculated. There were no pretest differences (P > 0.05) for any of these blood analytes between groups. The following, potentially, confounding variables were also measured: peak VO2, percent body fat (%BF), dietary composition, and habitual physical activity. These variables, with pretest HDL-C, were included as covariates in two-way split plot ANCOVA analyses. Dietary variables were not included as covariates as they were not related to any of the blood analytes. RESULTS: There were no differences over time or between groups for TG and TC (P > 0.05). LDL-C decreased in ET (-10.2%) but remained unchanged in CON (0.3%) over the intervention period (P < 0.05). HDL-C increased in ET (9.3%) but decreased in CON (-8.9%) (P < 0.01). A similar, but inverted, pattern of change (P < 0.01) was revealed for both ratios, TC/HDL-C (-11.6% vs 6.3%, ET and CON, respectively), and LDL-C/HDL-C (-17.2% vs 8.0%, ET and CON, respectively). The favorable alterations in the lipid-lipoprotein profile for ET were independent of alterations in peak VO2 (group x time interaction, P < 0.05), %BF (main effect time, P < 0.01), and habitual physical activity (group x time interaction, P < 0.01). CONCLUSIONS: In conclusion, the favorable alterations in the lipoprotein profile seen in this study would suggest that it is possible to influence the prepubertal lipoprotein profile independent of alterations in confounding variables such as body composition, cardiorespiratory fitness, and habitual physical activity.
Adipose Tissue↗
Frequent loss of heterozygosity on chromosomes 7 and 9 in benign epithelial ovarian tumours.
It is presently unclear if ovarian cancers arise through malignant transformation of pre-existing benign tumours. The apparent rarity of loss of heterozygosity (LOH) reported for benign tumours has led to speculation that they lack malignant potential and represent a biological entity distinct from ovarian carcinoma. We reasoned that the absence of detectable LOH may be due to the masking of such losses by contamination with normal tissue present in excess in the majority of benign tumour biopsies. Therefore we utilized a microdissection technique to examine for LOH using 14 microsatellite markers on chromosome arms 6q, 7p, 7q, 9p, 11q and 17p in 31 solitary benign epithelial ovarian tumours. LOH was detected on all chromosome arms with the most frequent LOH occurring on 7p (27%) and 9p (26%). In addition, a point mutation in codon 157 of TP53 was detected in one tumour which is the first report of a TP53 mutation in a solitary benign ovarian tumour. In total 48% of tumours harboured genetic alterations which supports the idea that all benign ovarian tumours may carry a genetic predisposition to malignancy and are therefore not inherently different from their malignant counterparts.
Chromosome Deletion↗
Loss of heterozygosity at the alpha-inhibin locus on chromosome 2q is not a feature of human granulosa cell tumors.
The alpha-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if alpha-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the alpha-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model alpha-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.
Adult↗
Thermoregulatory responses of paraplegic and able-bodied athletes at rest and during prolonged upper body exercise and passive recovery.
The thermoregulatory responses of ten paraplegic (PA; T3/4-L4) and nine able-bodied (AB) upper body trained athletes were examined at rest and during prolonged arm-cranking exercise and passive recovery. Exercise was performed for 90 min at 80% peak heart rate, and at 21.5 (1.7) degrees C and 47.0 (7.8)% relative humidity on a Monark cycle ergometer (Ergomedic 814E) adapted for arm exercise. Mean peak oxygen uptake values for the PA and AB athlete groups were 2.12 (0.41) min(-1) and 3.19 (0.38) l x min(-1), respectively (P<0.05). At rest, there was no difference in aural temperature between groups [36.2 (0.4) degrees C for both groups]. However, upper body skin temperatures for the PA athletes were approximately 1.0 degrees C warmer than for the AB athletes, whereas lower body skin temperatures were cooler than those for the AB athletes (1.3 degrees C and 2.7 degrees C for the thigh and calf, respectively). Upper and lower body skin temperatures for the AB athletes were similar. During exercise, blood lactate peaked after 15 min of exercise for both groups [3.33 (1.26) mmol x l(-1) and 4.30 (1.03) mmol x l(-1) for the PA and AB athletes, respectively, P<0.05] and decreased throughout the remainder of the exercise period. Aural temperature increased by 0.7 (0.5) degrees C and 0.6 (0.4) degrees C for the AB and PA athletes, respectively. Calf skin temperature for the PA athletes increased during exercise by 1.4 (2.8) degrees C (P<0.05), whereas a decrease of 0.8 (2.0) degrees C (P<0.05) was observed for the AB athletes. During the first 20 min of recovery from exercise, the calf skin temperature of the AB athletes decreased further [-2.6 (1.3) degrees C; P<0.05]. Weight losses and changes in plasma volume were similar for both groups [0.7 (0.5) kg and 0.7 (0.4) kg; 5.4 (4.9)% and 9.7 (6.2)% for the PA and AB athletes, respectively]. In conclusion, the results of this study suggest that the PA athletes exhibit different thermoregulatory responses at rest and during exercise and passive recovery to those of upper body trained AB athletes. Despite this, during 90 min of arm-crank exercise in a cool environment, the PA athletes appeared to be at no greater thermal risk than the AB athletes.
Adult↗
Coadministered pentobarbital anesthesia postpones but does not block the motor and sleep EEG responses to MK-801.
In previous studies with Sprague-Dawley rats, we demonstrated that NMDA channel blockade during waking massively stimulates the delta (1-4 Hz) EEG of non-rapid eye movement (NREM) sleep. However, non-competitive channel blockers also produce neurotoxicity that is manifested by posterior cingulate vacuolization and heat shock protein production. These neurotoxic effects can be blocked by coadministering gabaergic drugs, including barbiturates and benzodiazepines, with the MK-801. To determine whether delta stimulation by MK-801 would be similarly blocked, we administered an anesthetic dose (40 mg/kg) of pentobarbital followed immediately by 0.3 mg/kg of MK-801. Neither the MK-801 motor syndrome nor the NREM delta stimulation was blocked. When the rats recovered from nearly two hours of barbiturate anesthesia, they behaved as though they had just received the MK-801 injection, exhibiting the typical motor syndrome, spikes in the waking EEG and strong stimulation of NREM delta EEG. These findings support our previous evidence that NREM delta stimulation by NMDA channel blockade does not depend on toxic brain changes. They also raise interesting questions regarding the fate of MK-801 during pentobarbital anesthesia. We propose that the drug is not metabolized during the period of anesthesia because it is sequestered within the NMDA cation channel. However, neurons do not respond to the channel block because they have been rendered inert by the anesthesia. When the neurons emerge from anesthesia, the cascade of MK-801 events unfolds. This and other possible explanations can be tested experimentally. Establishing the fate of MK-801 during barbiturate anesthesia could shed new light on the cellular processing of non-competitive NMDA channel blockers.
Animals↗
No association of a 306-bp insertion polymorphism in the progesterone receptor gene with ovarian and breast cancer.
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Alleles↗
Determination of peak oxygen uptake during upper body exercise.
The purpose of this study was to determine (1) the repeatability of a currently recommended protocol for determination of VO2 peak during upper body exercise involving a crank rate of 60 rev min-1 (Hale et al. 1988), (2) whether employing a higher crank rate (70 rev min-1) elicits higher VO2 peak values; (3) whether including an additional exercise stage 5 min after volitional exhaustion would elicit higher VO2 peak values. Twenty subjects (mean +/- SD) age, height and body mass were 22.8 +/- 1.8 years, 176 +/- 5.0 cm and 77.5 +/- 4.0 kg, respectively) visited the laboratory on three separate occasions. Subjects performed a different test to determine upper body VO2 peak on each visit. The tests were continuous and incremental in nature and were performed on a Monark cycle ergometer (Model 814E) adapted for arm exercise. Test 1 required subjects to exercise at a crank rate of 60 rev min-1 (60RPM-1). Test 2 was identical to test 1 (60RPM-2) but after 5 min recovery from the test subjects performed a further exercise stage (60RPM-F). Test 3 employed a crank rate of 70 rev min-1 (70RPM). Five minutes after volitional exhaustion a further exercise stage was performed (70RPM-F). The levels of agreement for the 60 rev min-1 protocol were +/-0.50 1 min-1. All VO2 peak values achieved were within these limits. However, a higher VO2 peak was achieved by employing a crank rate of 70 rev min-1 (p < 0.05). The VO2 peak achieved for 60RPM-F was similar to 60RPM whereas the VO2 peak for 70RPM-F tended to be less than that for 70RPM (p = 0.064). The results of this study suggest that the 60 rev min-1 protocol can reliably determine VO2 peak, however it would appear to be more appropriate to employ a 70 rev min-1 protocol as higher values were attained.
Adult↗