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DNA functional groups required for formation of open complexes between Escherichia coli RNA polymerase and the lambda PR promoter. Identification via base analog substitutions.

Synthetic 75-base pair promoters bearing base changes and/or base analog substitutions at selected positions were constructed. Using both abortive initiation and run-off transcription assays, the interaction of these altered promoters with Escherichia coli RNA polymerase was studied in order to determine the involvement of DNA functional groups in promoter recognition. Two adjacent thymines in the -35 region were identified whose 5-methyl groups play a crucial role. Additionally, the combined results from several substitution experiments showed that functional groups in the major groove of the strongly conserved T-A base pair at the -7 position are probable sites of direct interaction with RNA polymerase.

Bacteriophage lambda↗

Myelographic study of the spinal cord ascent during fetal development.

To assess the length of the spinal cord relative to the vertebral column during fetal development, we performed translumbar myelograms on 340 spontaneously aborted fetuses. Of these, 146 were selected for study. There were 76 males and 70 females, with fetal age ranging from 7 to 33 weeks. Significant variation in the level of spinal cord termination was found in fetuses between 12 and 25 weeks gestational age. In fetuses between 25 and 33 weeks gestational age, the cord ended at or above the third lumbar vertebra.

Embryonic and Fetal Development↗

Intraoperative blood loss in midtrimester dilatation and extraction.

Intraoperative blood loss was evaluated in 215 patients undergoing a midtrimester dilatation and extraction procedure using a paracervical-intracervical block. Patients were assigned to four randomized drug regimens using a combination of 0.5% bupivacaine, dilute epinephrine, and methylergonovine maleate. From these four regimens, a select group of patients were given fentanyl. No significant difference in blood loss was observed in any group at less than 17 weeks' gestation. Only in gestations of 17 weeks or more was there a significant increase in blood loss, and this increase was associated specifically with the use of fentanyl in the nonrandomized selected group.

Abortion, Induced↗

The effect of bovine virus diarrhoea virus on reproduction in recently infected Norwegian dairy herds.

A group of 32 dairy herds, recently infected with bovine virus diarrhoea virus (BVDV), was compared with a control group consisting of 75 BVDV free herds during a 3-year-period. Variables related to reproduction were registered. Results of multiple antibody examinations in bulk milk as well as samples of milk and blood from younger animals were used to select the herds. The incidence of abortions was statistically significantly different in the 2 groups, while the number of stillbirths, weak born calves, and congenital anomalies was not. Other variables such as percentage of non return, average number of inseminations per cow and calving interval showed during the study a trend to improve in the BVDV group, while they remained stable in the control group.

Abortion, Veterinary↗

Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486).

Mifepristone (RU486), an 11beta-substituted nor-steroid containing a 17alpha-1-propynyl group used clinically as an antiprogestin agent for medical abortions, was demonstrated to be a selective mechanism-based inactivator of human cytochrome P-450-3A4 (CYP-3A4). The loss of testosterone 6beta-hydroxylation activity was time- and concentration-dependent as well as requiring metabolism of mifepristone in a purified CYP-3A4 reconstituted system. The inactivation exhibited pseudofirst-order kinetics. The values for KI and kinactivation were 4.7 microM and 0.089 min-1, respectively. The reduced-CO spectrum of CYP-3A4 was decreased by 76%, whereas approximately 81% of the activity was lost following incubation with mifepristone in the reconstituted system in the presence of NADPH. However, the Soret peak of the inactivated CYP-3A4 was slightly increased. High-performance liquid chromatography analysis of the incubation mixture showed that the peak containing the heme dissociated from the inactivated CYP3A4 was almost identical with that seen for the -NADPH control. Covalent binding of [3H]mifepristone to apoCYP3A4 was demonstrated by SDS-PAGE and high-pressure liquid chromatography analyses of the reconstituted system containing CYP-3A4, NADPH-CYP reductase, cytochrome b5 and lipids in the presence of NADPH. The stoichiometry was determined to be approximately 1 mol of mifepristone bound per 1 mol of CYP-3A4 inactivated. Therefore, the mechanism of inactivation of CYP-3A4 by mifepristone involves irreversible modification of the apoprotein at the enzyme active site instead of being the result of heme adduct formation or heme fragmentation. Mifepristone exhibits selectivity for CYP-3A4 as evidenced by the fact that it did not show mechanism-based inactivation of CYPs 1A, 2B, 2D6, and 2E1, although a competitive inhibition of CYP 2B1 and 2D6 was observed.

Abortifacient Agents, Steroidal↗

Unsafe abortions: methods used and characteristics of patients attending hospitals in Nairobi, Lima, and Manila.

Using quantitative and qualitative data, the authors present selected characteristics of 626 women who reported complications of induced abortion in five hospitals: one in Nairobi, two in Lima, and two in Manila. Although there are some similarities, the findings show some marked differences in demographic characteristics. In Nairobi nearly all respondents were single, nulliparous, and 25 years or younger; in Lima and Manila most were either married or in union, usually aged 25 years or older and had at least 1 child. There was evidence of repeat abortions, especially in Nairobi where 26% had had at least one previous abortion. Access to safe abortions is severely restricted and is obtained through a secret referral system. A list of potentially hazardous local abortifacients range from the drinking of strong Kenyan tea to dangerous practices such as insertion of sharp objects into the uterus or drinking chemicals and toxic substances.

Abortion, Illegal↗

Reproductive health services and the law and ethics of conscientious objection.

Reproductive health services address contraception, sterilization and abortion, and new technologies such as gamete selection and manipulation, in vitro fertilization and surrogate motherhood. Artificial fertility control and medically assisted reproduction are opposed by conservative religions and philosophies, whose adherents may object to participation. Physicians' conscientious objection to non-lifesaving interventions in pregnancy have long been accepted. Nurses' claims are less recognized, allowing nonparticipation in abortions but not refusal of patient preparation and aftercare. Objections of others in health-related activities, such as serving meals to abortion patients and typing abortion referral letters, have been disallowed. Pharmacists may claim refusal rights over fulfilling prescriptions for emergency (post-coital) contraceptives and drugs for medical (i.e. non-surgical) abortion. This paper addresses limits to conscientious objection to participation in reproductive health services, and conditions to which rights of objection may be subject. Individuals have human rights to freedom of religious conscience, but institutions, as artificial legal persons, may not claim this right.

Abortion, Induced↗

Medical versus surgical methods for first trimester termination of pregnancy.

BACKGROUND: Induced abortions are very commonly practiced interventions worldwide. A variety of medical abortion methods have been introduced during the last decade in addition to existing surgical methods. In this review we systematically searched for and combined all evidence from randomised controlled trials comparing surgical with medical abortion. OBJECTIVES: To evaluate medical methods in comparison to surgical methods for first-trimester abortion with respect to efficacy, side effects and acceptability. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (with the Cochrane 3-stage search strategy)(1966-2000) and Popline (1970-2000) were systematically searched. There were no language preferences in searching. Reference lists of retrieved papers were searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Randomised trials of any surgical abortion method compared with any medical abortion method in the first trimester. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was made independently by two reviewers. MAIN RESULTS: Five studies mostly with small sample sizes, comparing 4 different interventions (prostaglandins alone, mifepristone alone, and mifepristone/misoprostol and methotrexate/misoprostol versus vacuum aspiration) were included. Results are sometimes based on one trial only. Prostaglandins vs vacuum aspiration: the rate of abortions not completed with the intended method was statistically significant higher in the prostaglandin group (2.7, 95% CI 1.1 to 6.8) compared to surgery. There are no data on the most commonly medical (mifepristone/misoprostol) and surgical abortion available to be included in the review. Duration of bleeding was longer in the medical abortion groups compared to vacuum aspiration. There was only one major complication (uterine perforation) in one trial in the surgical group. There was no difference between the groups for ongoing pregnancies at the time of follow-up or pelvic infections. No data on acceptability, side effects or women's satisfaction with the procedure were available for inclusion in the review. REVIEWER'S CONCLUSIONS: The results are derived from small trials. Prostaglandins used alone seems to be less effective and more painful compared to surgical first-trimester abortion. However, there is inadequate evidence to comment on the acceptability and side effects of medical compared to surgical first-trimester abortions. There is a need for trials to address the efficacy of currently used methods and women's preferences more reliably.

Abortifacient Agents↗

Medical versus surgical methods for first trimester termination of pregnancy.

BACKGROUND: Induced abortions are very commonly practiced interventions worldwide. A variety of medical abortion methods have been introduced during the last decade in addition to existing surgical methods. In this review we systematically searched for and combined all evidence from randomised controlled trials comparing surgical with medical abortion. OBJECTIVES: To evaluate medical methods in comparison to surgical methods for first-trimester abortion with respect to efficacy, side effects and acceptability. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE (with the Cochrane 3-stage search strategy)(1966-2000) and Popline (1970-2000) were systematically searched. There were no language preferences in searching. Reference lists of retrieved papers were searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Randomised trials of any surgical abortion method compared with any medical abortion method in the first trimester. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was made independently by two reviewers. MAIN RESULTS: Six studies mostly with small sample sizes, comparing 4 different interventions (prostaglandins alone, mifepristone alone, and mifepristone/misoprostol and methotrexate/misoprostol versus vacuum aspiration) were included. Results are sometimes based on one trial only. Prostaglandins vs vacuum aspiration: the rate of abortions not completed with the intended method was statistically significant higher in the prostaglandin group (2.7, 95% CI 1.1 to 6.8) compared to surgery. There are no data on the most commonly medical (mifepristone/misoprostol) and surgical abortion available to be included in the review. Duration of bleeding was longer in the medical abortion groups compared to vacuum aspiration. There was only one major complication (uterine perforation) in one trial in the surgical group. There was no difference between the groups for ongoing pregnancies at the time of follow-up or pelvic infections. No data on acceptability, side effects or women's satisfaction with the procedure were available for inclusion in the review. AUTHORS' CONCLUSIONS: The results are derived from relatively small trials. Prostaglandins used alone seems to be less effective and more painful compared to surgical first-trimester abortion. However, there is inadequate evidence to comment on the acceptability and side effects of medical compared to surgical first-trimester abortions. There is a need for trials to address the efficacy of currently used methods and women's preferences more reliably.

Abortifacient Agents↗

Sexual activity, contraceptive practice and abortion among adolescents in Lagos, Nigeria.

Nine hundred fifty randomly selected secondary school girls were surveyed. Sexual activity was claimed by 29%, the youngest age was 12 years and age had no influence on the frequency of sexual intercourse. Multiple sexual partners, a high risk behaviour for contracting STD including AIDS was demonstrated in 33.7% and only 20.3% used orthodox methods of contraception. Induced abortion was procured by 23.5% and most were procured from unskilled personnel and by dangerous methods.

Abortion, Illegal↗

Induced abortions in low socio-economic settlements of Karachi, Pakistan: rates and women's perspectives.

OBJECTIVE: The aim of the study was to determine rates on induced abortions and to identify the perceived and actual reasons for terminating an unplanned pregnancy, health care providers sought, methods used and post-abortion complications. SETTING: Three squatter settlements of Karachi, Pakistan. SUBJECTS: Interviews were conducted on 1,214 ever-married women in the reproductive age group (15-49) with a reproductive history of at least one pregnancy, irrespective of outcome. METHODS: A cross-sectional survey from June-August 1997 was conducted in three selected squatter settlements of Karachi. RESULTS: The abortion rate for the past year was 25.5 per 1,000 women of reproductive age group. The post-abortion complication rate reported was 68.5% (61/89), of which fever and heavy vaginal bleeding was the most commonly reported complication (54.1%). CONCLUSION: The results indicate that women are aware of the high mortality and morbidity risk resulting from seeking an unsafe abortion but nevertheless opt for this approach to attain their goal of small family size rather than for a modern method of contraception. Furthermore, healthcare providers, irrespective of legality issues, provide such services due to demand. We suggest that family physicians and other relevant health care providers be trained for post-abortion care including post-abortion family planning counseling with an emphasis on emergency contraceptives.

Abortion, Induced↗

Equine herpesvirus type 1: detection of viral DNA sequences in aborted fetuses with the polymerase chain reaction.

Primers and probes were selected from the gene encoding glycoprotein 13 (gp 13) of equine herpesvirus 1 (EHV-1). The polymerase chain reaction (PCR) was run on infected and noninfected cultured cells and on 63 specimens from 29 aborted equine fetuses. The results were evaluated by electrophoresis and dot-blot hybridization using an oligonucleotide probe labeled with biotin. In the infected samples electrophoresis showed a PCR product of about 280 base pairs. The dot-blot hybridization confirmed that this product contained EHV-1 DNA sequences. PCR took 4 h and hybridization another 14 h; the results were thus achieved within 24 h and were highly specific for EHV-1. Close concordance was found between the results of PCR and virus isolation.

Abortion, Veterinary↗

Estimating clandestine abortion with the confidants method--results from Ouagadougou, Burkina Faso.

Data on abortion in sub-Saharan Africa are rare and non-representative. This study presents a new method to collect quantitative data on clandestine abortion, the confidants method, applied in 2001 in Ouagadougou, Burkina Faso. Preliminary qualitative work showed that individuals are aware of their close friends' induced abortions: women usually talk to their peers about the unintended pregnancy and ask them for help in locating illegal abortion providers. In a survey of 963 women of reproductive age representative of the city of Ouagadougou, we asked respondents to list their close relations, and, for each of them, and for each of the 5 years preceding the survey, whether they had an induced abortion. According to these data, there are 40 induced abortions per 1000 women aged 15-49 in Ouagadougou annually, and 60 per 1000 women aged 15-19. Adverse health consequences followed 60% of the reported induced abortions, and 14% of them received treatment in a hospital. Extrapolating these results to the entire city, we estimate that its hospitals treat about 1000 cases of abortion complications a year. Hospital data indicate that these centers admitted 984 induced abortions (adding all "certainly", "probably" and "possibly" induced abortions in the WHO protocol) in 2001; the age distribution of patients admitted for induced abortion also corresponds to the confidants method's projections ("certainly" induced abortions only). At least two biases could affect the abortion rates estimated by the confidants method, pertaining to the selection of the sample of relations and to the varying number of third parties involved in the abortion process. The confidants method, which is similar in its principle to the sisterhood method used to estimate maternal mortality levels, might generate accurate estimates of illegal abortion in certain contexts if these two biases are controlled for. Further testing is necessary.

Abortion, Illegal↗

Thinking outside the box: mechanisms of environmental selective pressures on the outcome of the materno-fetal relationship.

PROBLEM: Study of mechanisms causing spontaneous abortion of the vascularized placenta have focused primarily on the feto-maternal immunological relationship within the pregnant mother. The Th1 cytokines such as tumor necrosis factor (TNF)-alpha + interferon (IFN)-gamma derived in part from natural killer (NK) and NKgammadeltaT cells have been implicated in causing abortion via up-regulation of the novel prothrombinase fgl2 at the feto-maternal interface; Th2/3 cytokines such as interleukin (IL)-10, progesterone-induced blocking factor (PIBF), and TGF-beta2 derived from gammadeltaT cells stimulated by embryo antigens in the context of the OX-2 (CD200) tolerance signal have been viewed as counteracting the Th1 effect. These mechanisms are distinct from those causing and preventing occult pregnancy loss during the periimplantation phase of pregnancy prior to development of a vascularized placenta. Spontaneous abortions in the CBA/J x DBA/2 can be boosted by injecting TNF-alpha + IFN-gamma, but the boosted abortion rates can range from < or = 30 to > 80%, depending on the loss rate in uninjected mice, and this is not explainable by the endogenous level of these cytokines. Furthermore, there is a poor correlation between Th1/Th2.3 cytokine ratios and abortion rates. Could there be a third factor involved, and if so, what might this mean? METHODS: Known precipitants of recurrent abortion in mice were reviewed with particular attention to stress and endotoxin absorption. The effect of antagonizing the response to bacterial lipopolysaccharide (LPS) (endotoxin) was tested. Data on environmental selective pressures were considered (i.e. thinking outside the 'box', which typifies the conventional approach to thinking about materno-fetal interactions). RESULTS: Th1 cytokine-triggered abortions appear to depend on availability/presence of LPS. CONCLUSIONS: Environmental selective pressures are implicated in eliminating 'genetically weaker' embryos in early pregnancy.

Abortion, Habitual↗

Abortive intermediates in transcription by wheat-germ RNA polymerase II. Dynamic aspects of enzyme/template interactions in selection of the enzyme synthetic mode.

At constant enzyme concentration and with the full set of nucleotide substrates dictated by template sequence, the chain-length distribution of polymeric product varies with template concentration in reactions catalysed by wheat-germ RNA polymerase II. Under the same conditions, but in the presence of a single ribonucleoside triphosphate, the rate of condensation of the triphosphate substrate to a dinucleotide primer also exhibits a complex dependence with the template concentration. This effect is observed using poly[d(A-T)] as a template. For both reactions there are two extreme types of behaviour in each of which transcription appears to involve a single enzyme synthetic mode, characterized by either a high (at low template concentration) or a low (at high template concentration) probability of releasing the transcripts. A strong correlation is found between these two pathways, such that conditions favouring the abortive release of trinucleotide products in the single-step addition reaction are associated with the synthesis of short-length RNA species in productive elongation, and reciprocally. A model previously developed by Papanicolaou, Lecomte & Ninio [(1986) J. Mol. Biol. 189, 435-448] to account for the kinetics of polymerization/excision ratios with Escherichia coli DNA polymerase I, and by Job, Soulié, Job & Shire [(1988) J. Theor. Biol. 134, 273-289] for kinetics of RNA-chain elongation by wheat-germ RNA polymerase II provides an explanation for the observed behaviour with the plant transcriptase. The basic requirement of this model is a slow equilibrium between two states of the polymerization complex with distinct probabilities of releasing the product. In the presence of Mn2+, and under conditions allowing the synthesis of poly[r(A-U)], one of these states is involved in the formation of oligonucleotides shorter than 15 bases, whereas the other catalyses the polymerization of chains longer than 40 bases.

DNA↗

Abortive versus productive viral infection of dendritic cells with a paramyxovirus results in differential upregulation of select costimulatory molecules.

Dendritic cells are the most potent antigen-presenting cell for priming naive T cells. Optimal activation of T cells requires that dendritic cells undergo a process of maturation resulting in the increased expression of costimulatory molecules, such as CD40, CD86, and CD80, and the production of cytokines. In this study we analyzed the effect of infection of dendritic cells obtained from two strains of mice, BALB/c and C57BL/6, with the paramyxovirus simian virus 5 (SV5). Our results show that C57BL/6 bone marrow-derived dendritic cells (BMDC) are much more permissive to infection with SV5 at a multiplicity of infection (MOI) of 10 PFU/cell compared to BALB/c BMDC, as determined by the production of viral proteins and progeny. However, infection of BALB/c BMDC with a higher MOI of 50 PFU/cell resulted in a productive infection with the production of significant amounts of viral proteins and progeny. Regardless of the permissivity to infection, both BALB/c and C57BL/6 BMDC efficiently upregulated CD40 and CD86. However, CD80 upregulation correlated with the level of expression of viral proteins and the production of viral progeny. While secreted alpha/beta interferon was required for increased expression of all three molecules, optimal CD80 expression was dependent on an additional signal provided by a productive viral infection. These findings provide evidence that the signals controlling the expression of costimulatory molecules following viral infection are distinct. Further, they suggest that the amount of virus encountered and/or the permissivity of a dendritic cell to infection can alter the resulting maturation phenotype and functional capacity of the infected dendritic cell.

Animals↗