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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 145 records · Page 8Linked to original sources

Pregnancy smoking and childhood conduct problems: a causal association?

Recent investigations have highlighted associations between maternal smoking in pregnancy and antisocial behaviour in offspring, and suggested the possibility of a causal effect. We used data from the 1970 British birth cohort study (BCS70) to examine these links in a large. population-based sample studied prospectively from birth to age 16. We found a strong dose-response relationship between the extent of pregnancy smoking and childhood-onset conduct problems, but no links with adolescent-onset antisocial behaviours. Effects on childhood-onset conduct problems were as marked for girls as for boys, and were robust to controls for a variety of social background factors and maternal characteristics. Controls for mothers' subsequent smoking history modified this picture, however, suggesting that the prime risks for early-onset conduct problems may be associated with persistent maternal smoking--or correlates of persistent smoking--rather than with pregnancy smoking per se.

Adolescent↗

The Second Computer Assisted Telephone Interview (CATI) Forum: the state of play of CATI survey methods in Australia.

Computer Assisted Telephone Interview (CATI) systems are recognised in Australia and internationally for their ability to provide timely and relevant data on the health of the population. The Second CATI Population Health Surveys Forum highlighted the importance of this system for surveillance and using this information to determine priority health issues, develop strategies, monitor effectiveness of interventions, and influence health policy. A national CATI data collection strategy is required to determine priorities for health surveillance. Several development and technical issues need to be addressed for such a national strategy to provide a coordinated approach to health surveillance.

Australia↗

Hepatitis C virus among high and low risk pregnant women in Dundee: unlinked anonymous testing.

OBJECTIVE: To determine the prevalence of the hepatitis C virus among pregnant women, to gauge the non-injecting, particularly sexual, risk of them being hepatitis C virus infected and to assess the potential impact of selective antenatal screening. POPULATION: Antenatal clinic attenders and women undergoing termination of pregnancy in 1997. SETTING: Ninewells Hospital, Dundee. DESIGN: Unlinked anonymous hepatitis C virus antibody testing of residual sera from specimens sent to the virus laboratory for routine serological testing. The results were linked to non-identifying risk information. RESULTS: Overall anti-hepatitis C virus prevalence was 0.6% (23/3,548). Prevalences among injecting drug users, non-injectors who had a sexual partner who injected, and those with neither risk respectively were 41% (7/17), 15% (5/33) and 0.3% (11/3,498). Relative risks for being an injector and a sexual partner of an injector respectively were 131 (95% CI 58-297) and 48 (95% CI 5-32). It is estimated that one of the 18 antenatal clinic attenders gave birth to an infected child. CONCLUSION: Findings suggest that non-injecting partners of injectors may be at considerable risk of acquiring hepatitis C virus sexually. Efforts to promote the use of condoms among injectors and their sexual partners should be increased. Selective anti-hepatitis C virus screening of women who reported high risk behaviour would have failed to detect half the cases. Research to gauge the views of women of childbearing age on anti-hepatitis C virus testing is required.

Adult↗

Screening for HIV, hepatitis B and C infection in a population seeking assisted reproduction in an inner London hospital.

The Human Fertilisation and Embryology Authority requires all sperm donors to be screened for human immunodeficiency virus (HIV), hepatitis B and C and their semen quarantined for six months. No guidelines exist for screening prior to in vitro fertilisation or intracytoplasmic sperm injection. We prospectively analysed the prevalence of these viruses in our patients. Screening detected one case of HIV (0.13%), four of hepatitis C (0.5%) and 14 new cases of hepatitis B (1.7%). The prevalence of hepatitis B and HIV in our antenatal population at this time was 1.4% and 0.8%, respectively. Knowledge allows measures to be taken to reduce the risk of transmission to partner, fetus, new born baby, or by cross-contamination during embryo cryostorage and enables couples to make an informed decision regarding proceeding with treatment. Detection of infection in one partner should no longer preclude fertility treatment.

Female↗

Partner notification in HIV-1 infection: a population based evaluation of process and outcomes in Scotland.

OBJECTIVES: To evaluate the process and outcomes of HIV partner notification (PN) activity in Scotland. DESIGN: Retrospective population based study. SUBJECTS: 114 adults newly diagnosed with HIV infection (index patients) in Scotland between September 1995 and August 1996. SETTING: Healthcare settings in which all 114 new HIV diagnoses were made: 42 (37%) from genitourinary medicine; 32 (28%) infectious diseases; 18 (16%) general practice; and 22 (19%) from other sites. MAIN OUTCOME MEASURES: Number of partners notified and tested up to 9 months after initial diagnosis. RESULTS: Of 114 index patients (IPs), information on current partners was available for 102 (89%). PN was not appropriate for 47 of the 102 IPs. The remaining 55 IPs identified 63 current partners at risk, of whom 51 were notified: 44 underwent HIV testing, which yielded 11 new HIV positive diagnoses. Information on previous partners was available for only 56 IPs (49%). PN was not appropriate for 30 of the 56 IPs; the remaining 26 IPs identified 46 previous partners at risk, of whom 12 were notified: four were tested, but yielded no new diagnoses. CONCLUSIONS: Notification of current partners was performed well and was an effective strategy for identification of HIV positive individuals at a presymptomatic stage. Notification of previous partners was limited. Partner notification was attempted in a wide range of healthcare settings. Given the clinical effectiveness of antiretroviral therapy, partner notification as a tool towards early diagnosis of HIV disease deserves renewed attention.

Adult↗

NEM and filipin increase albumin transport in lung microvessels.

This study was undertaken to evaluate the role of transcytosis as a bulk transfer mechanism for the passage of albumin from blood to tissue. Isolated rat lungs were continuously weighed and perfused with an albumin-serum buffer solution under strictly controlled hemodynamic conditions, which allowed measurements of microvascular pressure and of the capillary filtration coefficient (L(p)S). With the use of a tissue uptake technique, it was possible to determine lung albumin clearance under isogravimetric conditions (Cl(iso)), or at elevated filtration rates, to obtain an "apparent albumin reflection coefficient" (sigma(alb)). Experiments were performed during control and after reducing lung temperature from 35 degrees to 22 degrees C and after infusions of the transcytosis inhibitors N-ethylmaleimide (NEM) or filipin. Cooling moderately increased vascular resistance and reduced L(p)S and Cl(iso) largely in proportion to the induced increases in viscosity. At 35 degrees C, NEM (0.13 mM) caused a marked increase in L(p)5 and in Cl(150) and also caused a reduction in sigma(alb.) Furthermore, Cl(iso) increased for the highest dose of filipin tested (1.8 microg/ml). The demonstrated relative cooling insensitivity of the transfer of albumin across the endothelium in rat lungs does not support the contention of transcytosis of proteins across the endothelium. Furthermore, neither NEM nor filipin inhibited lung microvascular albumin transport, but actually increased lung endothelial permeability.

Algorithms↗

Long-term facilitation in obstructive sleep apnea patients during NREM sleep.

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 +/- 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4-6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O(2) fraction (FI(O(2))) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing (n = 11), and supraglottic pressure (n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 +/- 8% of control), despite decreased Rua to 58 +/- 24% of control (P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.

Adult↗

Dynamics of inhibin subunit and follistatin mRNA during development of normal and polycystic ovary syndrome follicles.

To further explore the developmental dynamics and possible roles of inhibin, activin, and follistatin in the development of human antral follicles as well as the relationship between mRNA and protein levels of these hormones within follicles, quantitative competitive RT-PCR assays were established to determine mRNA levels for the inhibin/activin subunits and both follistatin splice variants. Granulosa cell RNA was obtained by transvaginally aspirating follicles (6-23 mm) from carefully characterized normal women at different times of the follicular phase. alpha- and beta(A)-subunit mRNA levels increased significantly with follicle diameter (r = 0.56; P < 0.01 and r = 0.45; P < 0.05, respectively) and follicle maturity (r = 0.65; P < 0.001 and r = 0.58; P < 0.01, respectively), but beta(B) mRNA levels, which were at least 10-fold lower than levels of the other subunits, showed no relationship to size or maturity. Both follistatin 315 and 288 transcripts were detected in granulosa cells, but neither follistatin transcript varied significantly across the range of follicle sizes analyzed. In addition, granulosa cells contained three follistatin 315 mRNA transcripts for each follistatin 288 transcript, and the follistatin 315/288 ratio did not vary with follicle size. alpha-Subunit mRNA levels were positively associated with dimeric inhibin A protein in human follicular fluid from the same follicle aspirates (r = 0.71; P < 0.001). Similarly, beta(A)-subunit mRNA was associated with inhibin A (r = 0.59; P < 0.01), and beta(B) mRNA was associated with inhibin B (r = 0.67; P < 0.005) in these samples. Thus, the increase in inhibin subunit transcription and protein synthesis with follicle size suggests that inhibin biosynthesis might be important for continued development of the dominant follicle. To explore this hypothesis further, we compared mRNA levels for each of these transcripts in follicles obtained from six polycystic ovary syndrome patients (eight follicles) and compared the results to those from a group (n = 5) of normal follicles matched for mean diameter. Comparisons were also performed for a subset of polycystic ovary syndrome follicles (n = 5) matched for diameter and size range with the normal group. alpha-Subunit mRNA levels were 16-fold lower in both polycystic ovary syndrome follicle groups relative to size-matched normal follicles (P < 0.02), whereas beta(A)-subunit mRNA was significantly lower only when all polycystic ovary syndrome follicles were compared. beta(B)-Subunit and follistatin mRNA levels and the follistatin 315/288 ratio were not statistically different for any group. These results suggest that insufficient production of inhibin alpha and possibly beta(A)-subunits, but not follistatin, is associated with follicular arrest in polycystic ovary syndrome follicles.

Actins↗

DnaK/DnaJ chaperone system reactivates endogenous E. coli thermostable FBP aldolase in vivo and in vitro; the effect is enhanced by GroE heat shock proteins.

Thermally aggregated, endogenous proteins in Escherichia coli cells form the S fraction, which is separable by sucrose density gradient centrifugation. To date, relatively little is known about the mechanisms of elimination of the heat-aggregated proteins from E. coli cells and the composition of the S fraction. We have identified several proteins of the S fraction using 2D-gel electrophoresis and microsequencing. A thermostable II class fructose-1,6-bisphosphate aldolase (Fda protein) appeared to be one of numerous proteins of the S fraction. Fda was purified from E. coli overproducer strain and used as a model substrate for investigation of the role of Hsps in prevention and repair of thermal denaturation of proteins both in vivo and in vitro. We found that the heat inactivation of Fda was reversible and that its reactivation in vivo and in vitro required mainly the assistance of the DnaK/DnaJ chaperone system. The dnaK756 and dnaJ259 mutations had a negative effect on the reactivation of thermally inactivated Fda. Moreover, we showed that the reactivation process in vitro was enhanced when GroEL/GroES were added together with DnaK/DnaJ. GroEL/GroES alone were inefficient in the resolubilization or reactivation of the heat-aggregated Fda. It is supposed that the denaturation of the thermostable Fda in vivo results rather from a temporary and transient deficit of Hsps than from the direct heat effect.

Cell Fractionation↗

The influence of environmental and genetic factors on behavior problems and autistic symptoms in boys and girls with fragile X syndrome.

OBJECTIVE: Fragile X syndrome, caused by mutations in a single gene of the X chromosome (FMR1), is associated with neurobehavioral characteristics including social deficits with peers, social withdrawal, gaze aversion, inattention, hyperactivity, anxiety, depression, and autistic behavior. However, there is considerable variability in the behavioral and psychiatric problems among children with this condition. The purpose of this study was to measure genetic and environmental factors influencing behavior problems and autistic symptoms in children with fragile X syndrome. DESIGN: We conducted an in-home evaluation of 120 children (80 boys and 40 girls) with the fragile X full mutation and their unaffected siblings, including measurements of the FMR1 protein (FMRP), quality of the home environment, maternal and paternal psychopathology, effectiveness of educational and therapeutic services, and child behavior problems. RESULTS: Results of multiple regression analyses showed that for boys with fragile X, effectiveness of educational and therapeutic services and parental psychological problems predicted internalizing and externalizing types of problems, while the quality of the home environment predicted autistic behavior. For girls with fragile X, the results emphasized significant effects of FMRP on behavior, in particular social withdrawal and anxious/depressed behavior. CONCLUSIONS: These findings are among the first to link FMRP expression to behavior. They also emphasize the significance of home- and school-based environmental variables in the neurobehavioral phenotype and help to lay the foundation for studies designed to identify specific interventions for reducing problem behavior in children with fragile X syndrome.

Adolescent↗

Hepatitis C virus among genitourinary clinic attenders in Scotland: unlinked anonymous testing.

Our objective is to gauge the prevalence of hepatitis C virus (HCV) antibodies among a population at risk of contracting sexually transmitted infections (STIs) and, thus, the efficiency with which the virus is transmitted sexually. The investigators undertook an unlinked anonymous HCV antibody testing study of residual syphilis serology specimens taken from attenders of genitourinary clinics in Glasgow, Edinburgh and Aberdeen during 1996/97. The results were linked to non-identifying risk information. Anti-HCV prevalences among non-injecting heterosexual men and women, and non-injecting homosexual/bisexual males ranged between 0 and 1.2%; the only exception to this was a 7.7% (4/52) prevalence among homosexual/bisexual males in Aberdeen. The overall anti-HCV prevalence for homosexual/bisexual males was 0.6% (4/668), for heterosexual males 0.8% (32/4135), for heterosexual females 0.3% (10/3035) and for injecting drug users 49% (72/148). Only 3 (all female) of the 46 non-injectors who were antibody positive were non-UK nationals or had lived abroad. HCV antibody positive injectors were less likely to have an acute STI and more likely to know their HCV status than non-injectors; no differences in these parameters were found between positive and negative non-injectors on anonymous HCV antibody testing. Our findings are in keeping with the prevailing view that HCV can be acquired through sexual intercourse but, for most people, the probability of this occurring is extremely low. Interventions to prevent the spread of HCV should be targeted mainly at injecting drug user (IDU) populations.

Female↗

Induction of the ubiquitin-proteasome pathway during the keratocyte transition to the repair fibroblast phenotype.

PURPOSE: To examine dynamics and function of the ubiquitin (Ub)-proteasome pathway (UPP) during corneal stromal cell acquisition of the repair fibroblast phenotype. METHODS: An established cell culture model was used in which freshly isolated rabbit corneal stromal cells acquire a repair fibroblast phenotype, thereby mimicking injury-induced stromal cell activation. RESULTS: Transition to the repair fibroblast phenotype during the 72 hours after initial plating was coincident with progressive UPP induction. Levels of Ub, Ub-conjugated proteins, ubiquitinylating enzymes E1 and E2-25K, and 26 S proteasome increased two- to fivefold in activated stromal cells. These increases were associated with enhanced (>10-fold) capacity for Ub-dependent proteolysis of (125)I-labeled H2A and with progressive (>6-fold) increases in the UPP substrate, inhibitor of kappaBalpha (IkappaBalpha). Because IkappaBalpha expression is induced by nuclear factor (NF)-kappaB, this finding suggests that rates of constitutive NF-kappaB activation, and thus IkappaBalpha degradation, are elevated in activated stromal cells. Both freshly isolated and activated stromal cells degraded IkappaBalpha in response to IL-1alpha; yet, only activated stromal cells maintained autocrine IL-1alpha expression after 24 hours. UPP induction was coincident with a more than 90% loss of tissue transketolase (TKT) and aldehyde dehydrogenase (ALDH) class 1. TKT was stabilized during the repair phenotype transition by proteasome inhibition and was degraded (>30%/h) by the UPP in cell-free assays. CONCLUSIONS: Coordinate induction of the UPP during stromal cell activation alters levels of IkappaBalpha and TKT, two UPP substrates that are implicated in the loss of tissue stasis and corneal clarity after injury.

Aldehyde Dehydrogenase↗

Distinctive patterns of static and dynamic gamma motor activity during locomotion in the decerebrate cat.

Simultaneous recordings were made from gamma (gamma) motor axons and from muscle spindle afferents of the medial gastrocnemius (MG) muscle during locomotion in decerebrate cats. The gamma-neurons were identified as static or dynamic (gammas or gammad) by correlating their behaviour during midbrain stimulation with changes in muscle spindle afferent responses to muscle stretch. On the basis of their behaviour during locomotion, gammas neurons could be divided into two groups. One group (type-1) showed strongly and smoothly modulated discharge increasing in parallel with the active muscle shortening in ankle extension, but with phase advance. The other group (type-2) also showed a modulated pattern, but with increased firing centred on the flexion phase. The proportions of the two were 13 type-1 and 7 type-2. The type-1 firing pattern accurately predicted the difference in firing frequency for secondary afferents obtained by subtracting from the recordings made during active movements the response of the same units to the movements repeated passively in the absence of fusimotor activity. The type-2 pattern also became consistent with the difference signal, when operated on by a phase lag appropriate to the effects of bag2 intrafusal fibres. These results suggest that there may be some degree of separate control of chain and bag2 intrafusal fibres. The discharge of gammad axons was also found to fluctuate with the locomotor cycle, with a pattern very distinct from that of the gammas records. The gammad firing frequency rose very suddenly from zero to a maximum at the onset of muscle shortening and continued into the beginning of lengthening. The term 'interrupted' discharge is suggested as a useful description. The timing of this discharge was shown to be appropriate for sensitising the primary afferents to detect the onset of stretch.

Animals↗