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Biomedical subjects

L Regan

Publications and source records attributed to L Regan.

14 recordsLinked to original sources
PubMed1992

Recurrent early pregnancy failure.

Some of the new developments that are improving our understanding of the mechanisms underlying recurrent early pregnancy failure are reviewed. Etiologies such as genetic causes, structural causes, chronic maternal disorders, drugs, environmental pollutants, endocrine causes, and immunologic causes are discussed, along with strategies for management.

Abortion, Habitual↗
PubMed1991

Protein design.

Several noteworthy papers have been published in the past year in which the creation of interesting novel proteins, either by de novo design or the redesign of existing proteins, has been reported. Highlights include the successful design of proteins for binding specific ligands.

Amino Acid Sequence↗
PubMed1991

A prospective study of the incidence, time of appearance and significance of anti-paternal lymphocytotoxic antibodies in human pregnancy.

The incidence and natural history of serum anti-paternal cytotoxic antibody (APCA) in normal pregnancy and spontaneous abortion was investigated prospectively in 306 women (64 primigravidae and 242 multigravidae), in order to establish whether serum APCA is a useful screening test in the diagnosis, treatment and prognosis for patients with recurrent pregnancy loss. Pre-pregnancy, serial pregnancy and post delivery serum samples were tested against partner's lymphocytes, using a microdroplet lymphocytotoxicity assay. The incidence of serum APCA in the 256 pregnancies successfully completed was 32%, compared with 10% amongst the 50 pregnancies ending in spontaneous abortion. The lower incidence of positive APCA tests in unsuccessful pregnancies was explained by our finding that positive APCA tests are related to the gestational age of the pregnancy and are rarely demonstrable before 28 weeks gestation. Since APCA usually disappears between pregnancies, its usefulness as a diagnostic test for immunotherapy against recurrent abortion should be questioned.

Abortion, Spontaneous↗
PubMed1990

A tetrahedral zinc(II)-binding site introduced into a designed protein.

The ultimate goal of protein engineering is to create novel proteins which will adopt predetermined structures, bind specified ligands, and catalyze new reactions. Here we describe the successful introduction of metal-binding activity into a model four helix bundle protein. The designed binding site is tetrahedral and is formed by two Cys and two His ligands on adjacent helices. We have introduced this site into the protein and characterized the binding activity. Using 65Zn(II), we have shown that the protein binds Zn(II), that the sulfhydryls are essential for binding, and that binding occurs to the protein monomer. The designed protein binds metals with high affinity: we estimate the dissociation constants as 2.5 X 10(-8) M for Zn(II) and 1.6 X 10(-5) M for Co(II). The characteristic absorption spectrum of the Co(II)-substituted protein fully supports the model of a tetrahedral binding site comprised of two Cys and two His ligands. Circular dichroism studies indicate that no significant changes in secondary structure occur between the metal-bound and metal-free forms of the protein. However, the metal-bound form is substantially stabilized toward denaturation by GuHCl compared to the metal-free form.

Amino Acid Sequence↗
PubMed1990

Hypersecretion of luteinising hormone, infertility, and miscarriage.

The relation between prepregnancy follicular-phase serum luteinising hormone (LH) concentrations and outcome of pregnancy was investigated prospectively in 193 women with regular spontaneous menstrual cycles. The group included 26 nulliparous and 167 multiparous women with various obstetric histories. Of the 147 women with LH concentrations of less than 10 IU/l (normal LH group) 130 (88%) conceived, whereas only 31 (67%) of the 46 women with LH values of 10 IU/l or more (high LH group) did so. In the high LH group, 20 (65%) of the pregnancies ended in miscarriage, whereas only 15 (12%) of pregnancies in the normal LH group did so. The adverse effect of a high prepregnancy LH concentration on fertility and outcome of pregnancy was seen in primigravidae, women with previously successful pregnancies, and women with a history of recurrent miscarriage. These data indicate an important role for hypersecretion of LH before conception in miscarriage. This finding offers the possibility of a simple predictive test for women before pregnancy, and could also be used to identify patients with an endocrine abnormality that can be remedied.

Abortion, Habitual↗
PubMed1990

A further look at infection at the time of therapeutic abortion.

Microbiological investigations and clinical follow-up were performed on 516 patients undergoing first-trimester termination of pregnancy, over a 2-year period. Chlamydia trachomatis was isolated by pre-operative microbiological screening in 6.7% of patients, gonococcus in 0.4% and Trichomonas vaginalis in 2%. Candida spp and Gardnerella vaginalis were isolated from 16% and 28% of the women, respectively. Patients who had positive cervical chlamydial isolation were significantly younger (less than 22 years) than those who did not. Doctor's clinical diagnosis of genital tract infection was found to be associated with a positive screening result but not with the likelihood of postabortal pelvic infection. Among the 175 patients followed up in the outpatient clinic, 4 of the 15 patients with a positive result for N. gonorrhoeae, C. trachomatis and/or T. vaginalis developed postoperative pelvic infection, which is significantly more than the group who did not harbour any of these three organisms (9/114).

Abortion, Therapeutic↗
PubMed1989

Influence of past reproductive performance on risk of spontaneous abortion.

OBJECTIVE: To investigate the incidence of spontaneous abortion in a population of women in order to establish their risk of spontaneous abortion and the obstetric factors predisposing to it. DESIGN: Prospective study of women recruited by radio and poster appeal and from hospital outpatient clinics. SETTING: English provincial community. PATIENTS: 630 Women from the general population intending to become pregnant. INTERVENTIONS: The viability of the pregnancy was assessed by abdominal ultrasonography before completion of the eighth week, and the assessment was repeated if vaginal bleeding occurred. MAIN OUTCOME MEASURE: Spontaneous abortion or live births in women with or without a previous history of spontaneous abortion. RESULTS: The overall incidence of clinically recognisable spontaneous abortion before 20 weeks of gestation was 12% (50/407 pregnancies). The risk of spontaneous abortion in each category of patient was classified with respect to the patient's past reproductive performance and found to be influenced greatly by her previous obstetric history. In primigravidas and women with a history of consistently successful pregnancies the incidences of abortion were low (5% (4/87) and 4% (3/73) respectively), whereas women with only unsuccessful histories had a much greater risk of aborting the study pregnancy (24% (24/98)), even when their sole pregnancy had ended in abortion (20% (12/59)). The outcome of the last pregnancy also influenced the outcome of the study pregnancy; only 5% of women (5/95) whose previous pregnancy had been successful aborted, whereas the incidence of loss of pregnancy among women whose last pregnancy had aborted was 19% (40/214). CONCLUSIONS: A knowledge of the patient's reproductive history is essential for the clinical assessment of her risk of spontaneous abortion. As the most important predictive factor for spontaneous abortion is a previous abortion, the outcome of a woman's first pregnancy has profound consequences for all subsequent pregnancies.

Abortion, Spontaneous↗
PubMed1987

Polypeptide sequences essential for RNA recognition by an enzyme.

Many RNAs are complex, globular molecules formed from elements of secondary and tertiary structure analogous to those found in proteins. Little is known about recognition of RNAs by proteins. In the case of transfer RNAs (tRNAs), considerable evidence suggests that elements dispersed in both the one- and three-dimensional structure are important for recognition by aminoacyl tRNA synthetases. Fragments of alanine tRNA synthetase were created by in vitro manipulations of the cloned alaS gene and examined for their interaction with alanine-specific tRNA. Sequences essential for recognition were located near the middle of the polypeptide, juxtaposed to the carboxyl-terminal side of the domain for aminoacyl adenylate synthesis. The most essential part of the tRNA interaction strength and specificity was dependent on a sequence of fewer than 100 amino acids. Within this sequence, and in the context of the proper conformation, a segment of no more than 17 amino acids was responsible for 25% or more of the total synthetase-tRNA free energy of association. The results raise the possibility that an important part of specific RNA recognition by an aminoacyl tRNA synthetase involves a polypeptide segment that is short relative to the total size of the protein.

Adenosine Triphosphate↗
PubMed1986

A bacterial and silkworm aminoacyl-tRNA synthetase have a common epitope which maps to the catalytic domain of each.

We report here the identification of a common immunological determinant in Escherichia coli and Bombyx mori (silkworm) alanine tRNA synthetases. The E. coli protein is a tetramer of identical Mr = 95,000 chains, and the silkworm enzyme is a monomer of Mr = 115,000. Antibodies against the silkworm enzyme react with E. coli Ala-tRNA synthetase. Analysis of 10 fragments of the E. coli enzyme has mapped the cross-reacting epitope to between amino acids 350 and 385. This is within the part of the enzyme which is essential for alanyladenylate synthesis. The anti-B. mori Ala-tRNA synthetase antibodies which cross-react with the E. coli enzyme were affinity-purified. They react specifically with the catalytic domain of the silkworm enzyme and not with the remaining dispensable segment of 500 amino acids. The results support the concept that the core catalytic structural elements, and not the dispensable portions, are the most related among the synthetases.

Alanine-tRNA Ligase↗