Biomedical subjects
Publications and source records attributed to Michael J Turner.
Substituted silacyclohexenes, generated through silene-diene [4 + 2] cycloaddition reactions, undergo Lewis acid promoted Sakurai type reactions with acetals to afford, following oxidation of the resultant fluorosilane, 1,4-diols with four contiguous chiral centres.
PURPOSE: It is currently unknown whether the age of wheel exposure influences running wheel activity in mice. The purpose of this study was to determine whether the age at which a running wheel was introduced affected running wheel activity for a subsequent 15-wk period. METHODS: Twenty female C57Bl/6J mice (age 7 wk) were assigned to one of four experimental groups. Group 1 received a running wheel at 7 wk of age. Thereafter, groups 2, 3, and 4 received running wheels at 10, 13, and 16 wk of age, respectively. Daily running wheel activity (duration, distance, and velocity) was recorded from the time of running wheel exposure until 30 wk of age. RESULTS: A repeated-measures MANOVA found significant differences between groups for distance (P = 0.02), duration (P = 0.04), and velocity (P = 0.001) during the 15-wk concurrent running period (age 16-30 wk). Post hoc tests revealed significantly greater distance and duration in group 4 compared with group 2 and significantly greater velocity in group 4 compared with each of the other groups. Significant interactions were found between groups over time for distance (P = 0.01) and duration (P = 0.05). No significant difference between groups was observed for body weight over the 24-wk period (P > 0.05). CONCLUSION: Although differences were found between groups 2 and 4, these data suggest that the age at which physical activity is introduced has little influence on the subsequent level of physical activity in C57Bl/6J mice. However, it appears that introduction of the running wheel at 16 wk of age results in greater within group variance, suggestive of a greater environmental influence on daily running wheel activity.
BACKGROUND: Due to the prevalence of prostate disease, there is a growing interest in the immunobiology of the prostate and its contribution to such pathologies. Further study is needed to fully characterize immune responses within the prostate. METHODS: Mouse ventral prostates were removed and analyzed using conventional immunohistochemistry, or by a novel whole mount technique, which allows the visualization of complete structures within the prostate. RESULTS: A lymphoid structure was detected within the base of the mouse ventral prostate. Whole mount and cryostat sections revealed an organized arrangement of lymphocytes, along with dendritic cells interspersed throughout the node. It possessed a rich network of lymph node specific high endothelial venules (HEVs) and adjoining lymphatics containing immune cells. CONCLUSIONS: Our results demonstrate the presence of a lymphoid structure within the base of the mouse ventral prostate possessing traits characteristic of an organized peripheral lymph node.
In humans, physical activity declines with age. We tested the hypothesis that genetic background and age interact to determine daily wheel-running physical activity patterns in mice. Five female mice from ten inbred strains (A/J, AKR/J, Balb/cJ, CBA/J, C3H/HeJ, C3Heb/FeJ, C57Bl/6J, C57L/J, DBA/2J, and SWR/J) were studied for 26 wk starting at 10 wk of age. All mice were housed in separate cages, each with a running wheel and magnetic sensor. Throughout the 26-wk period, age-related change in daily duration (P < 0.0001), daily distance (P < 0.0001), and average velocity (P = 0.0003) differed between the inbred strains. Unlike the other strains, SWR/J mice increased their running-wheel activity throughout the 6-mo time period. Broad-sense heritability estimations for the strains across the 26-wk period ranged between 0.410 and 0.855 for the three physical activity phenotypes. Furthermore, the broad-sense heritability estimates for daily running-wheel distance differed across time and suggested an interaction between genetic background and age on physical activity in these inbred mice.
This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7-15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days (3 wk). Average daily distance (km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance (P < 0.001), average daily exercise duration (P < 0.0001), and average daily exercise velocity (P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther (P = 0.01) and 38% faster (P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis (P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broad-sense heritability estimates on the physical activity differed by sex (for distance, male 31-48% and female 12-22%; for duration, male 44-61% and female 12-21%; for velocity, male 49-66% and female 44-61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex.
The contribution to the regulation of forearm blood flow (FBF) by different baroreceptor populations has previously only been studied over a limited range of stimuli. Therefore, FBF and R-R interval were recorded during neck suctions and neck pressures ranging from -60 to +40 mmHg. The change in R-R interval (DeltaR-R) during neck suction was significantly increased at each stage when compared to the control ( P<0.05). DeltaR-R did not show any significant change during any of the neck pressure stages ( P>0.05). Suction or pressure applied to the neck did not elicit any significant changes in FBF when compared to the control ( P>0.05). These data show that widening the range of applied stimuli to carotid sinus baroreceptors does not induce a change in FBF. However, the small transient changes reported previously cannot be discounted.
OBJECTIVE: To determine if the RhD status of the fetus can be detected in an unselected group of RhD-negative women with ongoing pregnancies booking for routine antenatal care. MATERIAL AND METHODS: We obtained 2.5 ml of whole blood from 202 unselected women with a normal ongoing pregnancy who booked for antenatal care before 20 weeks' gestation. DNA was extracted and real time quantitative PCR performed. Primers and a specific probe were targeted at the Rhesus D gene. RESULTS: Of 194 women, 31 were RhD-negative with no evidence of prior isoimmunisation. They delivered 17 RhD-positive and 14 RhD-negative babies. Of the 17 RhD-negative women carrying a RhD-positive fetus, the RhD gene was detected in the maternal blood in 14 (82%). There were no false positives. The quantity of RhD gene detected in the maternal blood of RhD-negative mothers ranged from 2 x 10(2) to 4 x 10(6) copies/ml of whole blood. CONCLUSION: Using real time quantitative PCR assays to amplify free fetal DNA in the maternal circulation, identification of RhD-positive fetuses in RhD-negative mothers is feasible when they book for antenatal care. Before such RhD genotyping can be introduced into clinical practice, however, further studies are required to show that false negative results can be eliminated and to show that this diagnostic test is reliable outside a research setting.
OBJECTIVES: To determine the incidence of maternal morbidity following elective caesarean section in women with a history of at least two previous caesarean sections, and to determine if the incidence of morbidity correlates with the number of previous sections. STUDY DESIGN: We conducted an individual chart review of all women who had an elective caesarean section because of a history of two previous sections from 1990 to 1999. RESULTS: There were 67,097 deliveries of babies weighing 500 g or more. The total number of cases eligible for the study was 250. There were 12 cases (4.8%) of placenta praevia of which four required a transfusion and two a hysterectomy. The incidence of wound infection was 6.3% and urinary tract infection was 11.2%. There were no cases of thromboembolism recorded. CONCLUSIONS: Maternal morbidity with elective repeat caesarean section is low. The major morbidity is associated with placenta praevia. We found no correlation between the incidence of maternal morbidity and the number of previous sections.
BACKGROUND: Human kallikrein 2 (hK2) and prostate-specific antigen (PSA) are serine proteases in the human kallikrein gene family that are 80% identical at the protein level. Like PSA, hK2 is expressed primarily in the prostate, making it an attractive bio-marker for prostate cancer development. In addition, its potent enzymatic activity may functionally affect the biology of prostate cancer. In order to further elucidate the possible roles of hK2 in prostate cancer, we have generated a panel of hK2-specific, non-PSA cross-reactive monoclonal antibodies. METHODS: A novel tumor-immunization strategy was used to produce monoclonal antibodies. Human hK2 cDNA was transfected into a BALB/c tumor cell line and used to immunize both BALB/c and PSA-expressing BALB/c.PSA transgenic mice. Because the BALB/c.PSA transgenic mouse showed a biased response towards hK2, a B cell fusion was performed using spleen cells from a transgenic mouse immunized in this fashion. RESULTS: A panel of monoclonal antibodies was produced and shown to be hK2-specific using newly developed hK2-specific sandwich ELISA and ELIspot assays. One of the monoclonal antibodies (6B7) was used to detect hK2 in human prostate by immunohistochemistry. Interestingly, two of the antibodies affected the function of hK2. The 1F8 antibody enhanced the enzymatic activity of hK2 whereas the 3C7 antibody inhibited its function. CONCLUSIONS: These hK2-specific antibodies illustrate a novel approach for constructing B-cell hybridomas and provide useful reagents to examine the role of hK2 in the biology and detection of prostate cancer.
Uterine rupture is an uncommon obstetric event. It is important because it continues to be associated with maternal mortality, especially in developing countries, and with major maternal morbidity, particularly peripartum hysterectomy. It is also associated with a high incidence of perinatal mortality and morbidity worldwide. This chapter examines the incidence, aetiology, clinical presentation, complications and prevention of uterine rupture. The key factor in the cause of rupture is whether or not the uterus is scarred. Rupture of an unscarred uterus is rare, usually traumatic, and its incidence decreases with improvement in obstetric practice. Rupture of the scarred uterus is more common, and usually occurs after a trial of labour in a patient with a previous Caesarean section. This chapter also explores how the incidence and complications of uterine rupture may be minimized, and yet the incidence of vaginal birth after Caesarean section (VBAC) optimized, in clinical practice.
OBJECTIVE: To determine the mode of the next delivery for primigravid women who have an elective caesarean section for breech presentation. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. POPULATION: All primigravid women who had an elective caesarean section for a singleton pregnancy in the years 1992 to 1997 and who delivered their next baby in the hospital before 1999. METHODS: Review of hospital computerised records. MAIN OUTCOME MEASURES: Mode of delivery and fetal presentation at next delivery. RESULTS: Of 194 women who had an elective caesarean section with a breech presentation as a primigravida, 19 (9.8%) had a breech presentation at the time of elective caesarean section for their next baby compared with only two (1.7%) in the 121 women who had an elective caesarean section with a cephalic presentation as a primigravida (RR 5.9 [95% CI 1.4-25.0]). Despite the increased likelihood of another breech presentation, the overall repeat section rate was 43.8% (n = 85) in women with a previous breech presentation (n = 194), compared with 61.2% (n = 74) in women with a previous cephalic presentation (n = 121) (RR 0.72 [95% CI 0.58-0.89]). Of those women allowed to labour after elective caesarean section as a primigravid, the vaginal birth rate was 109/130 (84%) if the presentation previously was breech compared with 47/69 (68%) if the presentation previously was cephalic (RR 1.2 [95% CI 1.03-1.50]). CONCLUSIONS: Women who have an elective caesarean section for a breech presentation in their first pregnancy have about a 1 in 10 chance of having an elective caesarean section for a breech presentation in their second pregnancy. Overall, the incidence of repeat caesarean section for their second baby was 43.8%, and of those allowed to labour, 84% achieved a vaginal delivery. These results compared favourably with women who had an elective caesarean section with a cephalic presentation in their first pregnancy. This information is important in advising primigravid women with a breech presentation about longer term implications of elective caesarean section. It also allows healthcare managers to anticipate the resource implications of any changes in clinical practice for women with a breech presentation in their first pregnancy.