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C Flanagan

Publications and source records attributed to C Flanagan.

18 recordsLinked to original sources
PubMed2026

Obtaining a Diagnostic Yield via Scan findings prior to the introduction of SEquencing retrospectivelY (ODYSSEY): a cohort study.

OBJECTIVE: To determine the retrospective yield of prenatal exome sequencing (PES) by establishing the proportion of children with a postnatal monogenic diagnosis that could have been diagnosed prenatally if PES had been available. METHODS: The study cohort comprised a sample of children in Northern Ireland, born between January 2010 and January 2018 (predating routine availability of PES), who received a monogenic diagnosis postnatally via next generation sequencing as part of either of two UK-wide studies (the 100 000 Genomes Project (2015-2018) or the Deciphering Developmental Disorders study (2011-2015)). Clinical data were collected retrospectively and correlated with the current UK National Health Service PES protocol, including the phenotypic eligibility criteria for PES and the associated fetal anomalies gene panel. Cases were considered retrospective diagnoses if the fetal phenotype would have been eligible for PES and the diagnostic gene was included on the test panel, meaning prenatal diagnosis in this current era could have been feasible. RESULTS: Of 101 children, 17.8% (95% CI, 10.3-25.3%) had both an eligible fetal structural anomaly (FSA) (i.e. high-risk FSA) and a diagnostic gene on the associated test panel, meaning that they could have been diagnosed prenatally in the current clinical landscape. The median length of the diagnostic odyssey for this subgroup of children was 3.7 years (1354 (range, 822-2450) days). Moreover, 58.4% (n = 59) of cases had no anomalies detected prenatally and 19.8% (n = 20) had a FSA that would not meet the eligibility criteria for PES (low-risk FSA). Although these cases would have been ineligible for PES under the current clinical pathway, 89.9% (n = 71/79) were affected by severe or profound syndromes. Postnatally, the most common functional anomalies were neurodevelopmental delay/intellectual disability and/or behavioral abnormality, which were observed in 80.2% (n = 81) of the included children. However, 80.2% (n = 65/81) of these affected children did not present with fetal anomalies eligible for PES. CONCLUSIONS: Almost one-fifth of children with a monogenic condition included in this study could have received a diagnosis via modern PES, avoiding a diagnostic odyssey lasting almost 4 years. However, despite having a monogenic condition, over half of the children did not present with any structural anomalies in utero. This demonstrates the degree to which fetal imaging is limited in its ability to reassure parents of the absence of a fetal genetic syndrome. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Humans↗
PubMed1996

Structural requirements for alpha-mating factor activity.

The sexual hormone of S. cerevisiae, alpha-mating factor (alpha-MF, WHWLQLKPGQPMY) has structural homology with mammalian luteinizing hormone releasing hormone (LHRH, pEHWSYGLRPG-NH2) and has been shown to exhibit LHRH activity [Loumaye et al. (1982) Science 218, 1323-1325]. We have tested whether LHRH has alpha-MF activity in yeast and found that it does not. We therefore synthesized a series of hybrid peptides of alpha-MF and LHRH to study the structural features which determine alpha-MF and LHRH activities. A hybrid peptide consisting of the LHRH sequence with the C-terminal tetrapeptide (QPMY) of alpha-MF did not exhibit alpha-MF activity. Thus, the lack of alpha-MF activity of LHRH is not due solely to the absence of the C-terminal residues. Substitution of Lys7 in alpha-MF with Arg, as is found in LHRH, did not affect the alpha-MF activity, nor did an additional substitution of Trp1 with pGlu. However, the C-terminal four amino acids of alpha-MF were necessary for alpha-MF activity. Our results indicate that insertion of a Ser residue in position 4 as found in LHRH abolishes alpha-MF activity. These results suggest that, in addition to an intact C-terminus, correct spacing of the N-terminal His2 and the C-terminus is required for alpha-MF activity. The hybrid peptides all exhibited less LHRH activity than either LHRH or alpha-MF. These structure-function studies indicate that the structural homology between these two reproductive hormones may not reflect an evolutionary relationship between them.

Amino Acid Sequence↗
PubMed1996

Schools, families, and early adolescents: what are we doing wrong and what can we do instead?

Although most individuals pass through adolescence without excessively high levels of "storm and stress," many individuals experience difficulty during this period. Why? Is there something unique about this developmental period that puts individuals at greater risk for difficulty? This paper focuses on these questions and advances the hypothesis that some of the "negative" psychological and behavioral changes associated with adolescent development result from a mismatch between the needs of developing adolescents and their experiences at school and at home. It provides theoretical and empirical examples of how this mismatch develops, how it is linked to negative age-related changes in early adolescents' motivation, self-perceptions, self-evaluations, and psychological competence, and how we could provide more developmentally appropriate social environments, particularly at school.

Adolescent↗
PubMed1994

A reciprocal mutation supports helix 2 and helix 7 proximity in the gonadotropin-releasing hormone receptor.

Activation of the pituitary gonadotropin-releasing hormone receptor, a member of the seven-transmembrane G protein-coupled receptor (GPCR) family, triggers a cascade of events leading to gonadotropin release and stimulation of the reproductive system. An unusual feature of this receptor, observed in mice, rats, and humans, is the presence of Asn87 in the second putative transmembrane helix at the location of a highly conserved aspartate in the GPCR family and of Asp318 in the putative seventh transmembrane helix where nearly all other GPCRs have asparagine. The possibility that these residues interact was suggested by this reciprocal pattern and by a three-dimensional model of the gonadotropin-releasing hormone receptor and was investigated by site-directed mutagenesis. Replacing Asn87 in the second transmembrane domain by aspartate eliminated detectable ligand binding. A second mutation, generating the double-mutant receptor Asp87Asn318, recreated the arrangement found in other GPCRs and re-established high affinity agonist and antagonist binding. The restoration of binding by a reciprocal mutation indicates that these two specific residues in helices 2 and 7 are adjacent in space and provides an empirical basis to refine the model of the transmembrane helix bundle of the receptor.

Amino Acid Sequence↗
PubMed1993

Cloning and characterization of the human GnRH receptor.

A cDNA encoding the human GnRH receptor (GnRHR) has been cloned and functionally expressed in both Xenopus oocytes and COS-1 cells. The 2160 bp cDNA encodes a 328 amino acid protein with a predicted amino acid sequence that is 90% identical to that of the mouse GnRHR (Tsutsumi et al. (1992) Mol. Endocrinol. 6, 1163-1169). Injection of synthetic RNA transcript into oocytes led to the development of a depolarizing response to agonists when assayed by voltage-clamp electrophysiology. Consistent with the expression of a mammalian GnRHR, the response was blocked by GnRH antagonists. Following expression of the human GnRHR in COS-1 cells, agonists and an antagonist displaced [125I]GnRH agonist from membrane isolates with nanomolar range dissociation constants similar to those described for displacement from human pituitary membranes. Transfected COS-1 cells manifested a GnRH-stimulated increase in phosphoinositol turnover, with an EC50 of approximately 3 nM, which was inhibited by GnRH antagonists. Northern blot analysis revealed a single band of approximately 4.7 kb expressed in human pituitary which was not detected in testis. The predicted structure of the human GnRHR is similar to that previously reported for the mouse receptor. Although the mammalian GnRHR is a seven transmembrane domain receptor, it differs from other G-protein coupled receptors in several respects, most notably the lack of a cytoplasmic C-terminal domain. The present study demonstrates that the cDNA isolated encodes the human GnRHR and suggests that several unique features conserved among mammalian GnRHRs may be essential for receptor function and/or regulatory control.

Amino Acid Sequence↗
PubMed1993

Development during adolescence. The impact of stage-environment fit on young adolescents' experiences in schools and in families.

Although most individuals pass through adolescence without excessively high levels of "storm and stress," many do experience difficulty. Why? Is there something unique about this developmental period that puts adolescents at risk for difficulty? This article focuses on this question and advances the hypothesis that some of the negative psychological changes associated with adolescent development result from a mismatch between the needs of developing adolescents and the opportunities afforded them by their social environments. It provides examples of how this mismatch develops in the school and in the home and how it is linked to negative age-related changes in early adolescents' motivation and self-perceptions. Ways in which more developmentally appropriate social environments can be created are discussed.

Adolescent↗
PubMed1991

The use of intraaortic balloon pumping as an adjunct to reperfusion therapy in acute myocardial infarction. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group.

To assess the risk and possible benefits of use of the percutaneous IABP in patients given thrombolytic therapy as treatment for acute myocardial infarction, we prospectively evaluated 810 consecutive patients entered into the TAMI trials. During hospitalization the 85 patients treated with the IABP had more cardiac risk factors, were slightly older (58 vs 56 years), and more often had anterior infarction (62% vs 38%). At acute cardiac catheterization, patients treated with the IABP also had more multivessel coronary disease (67% vs 43%), more frequent TIMI grade 0 or 1 flow (44% vs 28%), lower global ejection fraction (40% vs 52%), and worse regional infarct (-3.2 vs -2.5 SD/chord) and noninfarct (-0.67 vs +0.36 SD/chord) zone function. Although mortality rates (32% vs 4%) and in-hospital complications were greater in patients treated with the IABP, a greater improvement in global (delta ejection fraction: +1.9% vs +0.7%) and noninfarct zone (delta SD/chord: +0.11 vs -0.09) left ventricular function was observed in patients treated with the IABP at 1-week follow-up angiography. In addition, no reinfarction or reocclusion of the infarct-related artery occurred while patients were being treated with the IABP. These results suggest that the IABP may have a specific role after thrombolytic therapy in treating patients at high risk for reocclusion or at high risk for hemodynamic deterioration because of large infarction or critical stenoses in coronary vessels supplying the noninfarct zone.

Angioplasty, Balloon, Coronary↗
PubMed1991

Comparison of the activity of cefixime and activities of other oral antibiotics against adult clinical isolates of Moraxella (Branhamella) catarrhalis containing BRO-1 and BRO-2 and Haemophilus influenzae.

MICs of 10 oral antibiotics were determined for 105 Moraxella catarrhalis and 96 Haemophilus influenzae isolates from adults. A two- to fourfold increase in MICs of oral cephalosporins was seen in the presence of BRO-1 but not with TEM-1 or BRO-2. The MICs of cefixime for 90% of strains of H. influenzae (0.125 microgram/ml) and M. catarrhalis (0.25 microgram/ml) were 8- to 64-fold lower than those of other oral cephalosporins.

Administration, Oral↗
PubMed1989

BRO beta-lactamases of Branhamella catarrhalis and Moraxella subgenus Moraxella, including evidence for chromosomal beta-lactamase transfer by conjugation in B. catarrhalis, M. nonliquefaciens, and M. lacunata.

Two closely related beta-lactamases, BRO-1 and BRO-2 (formerly called Ravasio and 1908), are found in Moraxella (Branhamella) catarrhalis. We screened strains of B. catarrhalis recovered in the United States since 1952 and identified the first beta-lactamase-positive isolate in August 1976. The prevalence of the enzymes among 394 clinical isolates from one Texas hospital has averaged 75% since testing began in 1983. Screening of isolates of Moraxella subgenus Moraxella revealed the BRO enzymes in two other human respiratory tract species, M. lacunata and M. nonliquefaciens, beginning in 1978. A different beta-lactamase with a pI of 6.4 predominated in other species of subgenus Moraxella. BRO-2 had a different isoelectric focusing pattern and was produced in lesser amounts than BRO-1, but the two enzymes were indistinguishable by substrate or inhibitor profile. BRO enzymes from B. catarrhalis, M. nonliquefaciens, and M. lacunata could be transferred by conjugation and, for B. catarrhalis, also by transformation to B. catarrhalis. Plasmid bands were demonstrated in 90% of M. nonliquefaciens and in one previously reported strain of B. catarrhalis, but no change in plasmid profiles was seen in beta-lactamase-positive recombinants, supporting previous studies that suggested the beta-lactamase genes are chromosomal.

Chromosomes, Bacterial↗
PubMed1979

Efficacy of Stenorol (halofuginone). I. Against recent field isolates of six species of chicken coccidia.

The efficacy of Stenorol (halofunginone) was tested against six species of chicken Eimeria in a series of four battery experiments utilizing 3- to 4 1/2-week-old Cobb color-sexed broiler chickens. There were five replicates of eight chickens per replicate for each treatment of an experiment or a total of 1080 birds used in the study. The isolates were predominantly E. tenella, E. maxima, E. acevulina, E. necatrix, E. brunetti, or E. mivati and had previously been proven partially to totally resistant to several commercially available anticoccidial drugs. Halofunginone, at 3 ppm in the ration, was highly effective (P less than .01) against all six isolates as measured by weight gain at D+6 or +7and D+12 or +14 postinoculation; feed efficiency at D-2 to D+12 or +14; morbidity; mortality; dropping score; lesion score (D+6 or +7); and oocyst production during 4 or 5 days postinoculation (D = day of inoculation). The drug was not as effective against E. acervulina as against the other species, and increasing halofuginone to 4 ppm failed to improve activity of the drug signif;cantly against this isolate. However, 3 ppm of drug was effective against two other isolates of E. acervulina (from Alabama and Mississippi); 4 ppm was quite effective (P less than .01) in reducing dropping and lesion scores, but not significantly better than 3 ppm as measureed by other parameters. No relapse occurred after drug withdrawal and halofuginone was found to be cidal rather than static.

Animals↗
PubMed1979

Efficacy of Stenorol (halofuginone). II. Plus roxarsone or bacitracin MD against selected strains of chicken Eimeria.

A total of 879 broiler strain chickens ranging from 2 1/2- to 7 1/2 weeks of age was utilized in four battery experiments to determine whether Roxarsone and/or bacitracin MD added to halofuginone were compatible and beneficial in reducing the effects of coccidial infections. The additives were generally beneficial as measured by weight gain and feed efficiency but not as measured by other parameters such as dropping score, lesion score, or oocyst production. The addition of 200 g of bacitracin/ton of feed did not give an additional response above that from 50 g/ton. Roxarsone in the ration was more effective in younger chickens (2 1/2 week old) than older ones (6 weeks, 2 days and 7 weeks, 3 days).

Animals↗
PubMed1979

Efficacy of Stenorol (halofuginone). III. for the control of coccidiosis in turkeys.

Halofuginone at 3 ppm in the ration was tested against turkey coccidial infections caused by four species, in a series of eight battery trials of 16 days duration. The drug was evaluated against infections caused by Eimeria meleagrimitis, E. adenoeides, E. gallopavonis, and E. dispersa. As measured by livability, weight gain, feed efficiency, morbidity, dropping score, lesion score, and oocyst production the drug was highly effective in Beltsville Small White turkeys. The drug at 3 ppm appeared to be about equally effective against all four species and almost completely prevented infection or the effects of infection in some experiments, except when the challenge was too severe.

Animals↗
PubMed1978

Activating and anesthetic effects of general depressants.

The long-sleep (LS) and short-sleep (SS) lines of mice were derived by selective breeding with respect to ethanol sleep time. We found that in current generations LS mice also have longer sleep times than SS mice to trichloroethanol and paraldehyde. Two subsequent experiments tested our hypothesis that mice that are relatively insensitive to the hypnotic effects of depressant drugs might be relatively activated by low doses of these drugs. Both experiments failed to support the hypothesis. First, although SS mice were more activated than LS mice by subhypnotic doses of paraldehyde, the lines did not differ in the degree of activation produced by low doses of trichloroethanol. Second, among mice from a genetically heterogeneous population (HS), there was no relation between the degree of activation induced by a low dose of ethanol and sensitivity to the hypnotic effects of a higher dose.

Animals↗
PubMed1977

In vitro adsorption of doxorubicin hydrochloride on insoluble calcium phosphate.

The adsorption of doxorubicin hydrochloride, a potent antitumor agent, on solid tribasic calcium phosphate was studied in vitro. A Langmuir adsorption isotherm at pH 7.4 and the maximum adsorption capacity of tribasic calcium phosphate were established. Tribasic calcium phosphate was chosen as a model for solid bone samples, which are stained with doxorubicin in patients who have received long-term doxorubicin therapy.

Adsorption↗
PubMedDate not supplied

Seasons and depression: the influence of cigarette smoking.

The seasonality of depressive illness has been documented since antiquity. A review of 611 patients, who were consecutively admitted to the adult inpatient psychiatric unit of a mid-Michigan general hospital, examined the influence of cigarette smoking and psychiatric diagnosis upon the seasonal variation of admissions. Among the smokers, admissions for depressive disorders (n = 151) peaked in the springtime (z = 2.1, p < .05) and declined in summer. Admissions for the nonsmokers failed to demonstrate a substantial seasonal rhythm. Admissions for smokers and nonsmokers in other diagnostic groups did not show any seasonal variation. These findings parallel numerous studies regarding the influence of seasons upon rates of hospitalization for depressive disorder, and completed suicide. Therapeutic implications related to the bidirectional relationship between cigarette smoking and depression are discussed.

Adult↗