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Biomedical subjects

J Dornan

Publications and source records attributed to J Dornan.

At least 19 recordsLinked to original sources
PubMed2005

Admission to neonatal intensive care with respiratory morbidity following 'term' elective caesarean section.

Delaying the timing of elective caesarean section (ELCS) from 37/38 weeks to 39/40 weeks reduces the risk of respiratory morbidity in otherwise healthy neonates. The aims of this study were to clarify the number and clinical details of term infants delivered by ELCS who were admitted to neonatal intensive care (NIC) from 1st April 2001 to 31st March 2002 in Northern Ireland, to record the level of care required by these infants and to identify infants who were diagnosed with transient tachypnoea of the newborn (TTN) and/or Respiratory Distress Syndrome (RDS). Two hundred and ten (8%) of babies born by ELCS were admitted to NIC. Term infants delivered by ELCS used 343 days of level 1 & 2 care with 230 (68%) of these days being used by infants with RDS/TTN (n=105) the majority of whom were delivered at 37/38 weeks. Definitions of 'term' and clinical indications for ELCS urgently need to be debated to avoid unnecessary morbidity following ELCS in so called 'term' infants.

Cesarean Section↗
PubMed2003

Techniques and materials for skin closure in caesarean section.

BACKGROUND: Caesarean section is a common operation with no agreed standard on operative techniques and materials to use. The skin layer can be repaired by sub cuticular stitch immediately below the skin layer, an interrupted stitch or with skin staples. A great variety of materials and techniques are used for skin closure after caesarean section and there is a need to identify which provide the best outcomes for women. OBJECTIVES: To compare the effects of skin closure techniques and materials on maternal outcomes and time taken to perform a caesarean section. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (August 2002). SELECTION CRITERIA: All randomised comparisons of skin closure techniques in caesarean section. DATA COLLECTION AND ANALYSIS: Three papers were identified from the search. Data were extracted independently by two reviewers. On further inspection two were not considered to be randomised controlled trials. MAIN RESULTS: Only one small randomised controlled trial, involving 66 women, was included in the review. Frishman et al compared staples with absorbable sub-cuticular suture for closure following caesarean section. While operating time was significantly shorter when using staples, the use of absorbable sub cuticular suture resulted in less postoperative pain and yielded a better cosmetic result at the post-operative visit. REVIEWER'S CONCLUSIONS: There is no conclusive evidence about how the skin should be closed after caesarean section. Questions regarding the best closure technique and material and the outcomes associated with each remain unanswered. The appearance and strength of the scar following caesarean section is important to women and the choice of technique and materials should be made by women in consultation with their obstetrician based on the limited information currently available.

Cesarean Section↗
PubMed2001

Crystallization and preliminary X-ray analysis of ocr, the product of gene 0.3 of bacteriophage T7.

Ocr, the product of gene 0.3 of bacteriophage T7, prevents the action of restriction endonucleases of the host bacteria. The amino-acid sequence of ocr has less than 20% similarity to any protein of known three-dimensional structure. Ocr has been crystallized in a number of different crystal forms and X-ray data for the seleno-L-methionine-substituted form has been collected to a resolution of 1.8 A. The presence of caesium was found to be required for good crystal growth. Anomalous X-ray data was used to identify possible positions for Se and Cs atoms in the unit cell.

Amino Acid Sequence↗
PubMed2001

Two structures of cyclophilin 40: folding and fidelity in the TPR domains.

BACKGROUND: The "large immunophilin" family consists of domains of cyclophilin or FK506 binding protein linked to a tetratricopeptide (TPR) domain. They are intimately associated with steroid receptor complexes and bind to the C-terminal domain of Hsp90 via the TPR domain. The competitive binding of specific large immunophilins and other TPR-Hsp90 proteins provides a regulatory mechanism for Hsp90 chaperone activity. RESULTS: We have solved the X-ray structures of monoclinic and tetragonal forms of Cyp40. In the monoclinic form, the TPR domain consists of seven helices of variable length incorporating three TPR motifs, which provide a convincing binding surface for the Hsp90 C-terminal MEEVD sequence. The C-terminal residues of Cyp40 protrude out beyond the body of the TPR domain to form a charged helix-the putative calmodulin binding site. However, in the tetragonal form, two of the TPR helices have straightened out to form one extended helix, providing a dramatically different conformation of the molecule. CONCLUSIONS: The X-ray structures are consistent with the role of Cyclophilin 40 as a multifunctional signaling protein involved in a variety of protein-protein interactions. The intermolecular helix-helix interactions in the tetragonal form mimic the intramolecular interactions found in the fully folded monoclinic form. These conserved intra- and intermolecular TPR-TPR interactions are illustrative of a high-fidelity recognition mechanism. The two structures also open up the possibility that partially folded forms of TPR may be important in domain swapping and protein recognition.

Amino Acid Sequence↗
PubMed1999

Biochemical and structural characterization of a divergent loop cyclophilin from Caenorhabditis elegans.

Cyclophilin 3 (CYP-3) is one of the most abundantly expressed cyclophilin isoforms in the free living nematode Caenorhabditis elegans. The detailed post-embryonic expression pattern of the cyp-3 transcript is unusual, peaking during early larval development. The spatial expression pattern was examined via reporter gene analysis demonstrating that the cyp-3 transcript is exclusively expressed in the single anterior excretory cell. Recombinant cyclophilin 3 has been purified, crystallized and solved to a resolution of 1.8 A. The peptidyl-prolyl isomerase activity of CYP-3 has been characterized against the substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, and gives a k(cat)/K(m) value of 2.4 x 10(6) M(-1) s(-1). The immunosuppressive drug cyclosporin A binds and inhibits CYP-3 with an IC(50) value of 16 nM, comparable with the range of values found for human cyclophilin A. The x-ray structure shows that the overall fold and active site geometry is similar to other cyclophilin structures. There are however a number of distinctive features, and we use this structure and amino acid sequence alignment analysis to identify a subgroup of "divergent-loop cyclophilins". This subgroup has a number of uniquely conserved features: an additional loop between residues 48 and 54 (KSGKPLH); two cysteine residues (Cys(40) and Cys(168)) that are in close proximity but remain in the unoxidized form, and two other conserved residues, His(54) and Glu(83). We suggest that these features are functionally important for the role played by this class of cyclophilins during cellular responses to stress caused by changes in the redox environment or by up-regulation of cellular activity. This study represents a detailed biological, biochemical, and structural characterization of a single cyclophilin isoform in the model organism Caenorhabditis elegans.

Amino Acid Sequence↗
PubMed1999

Purification, characterization and crystallization in two crystal forms of bovine cyclophilin 40.

The purification and crystallization of two different crystal forms of the two-domain protein bovine cyclophilin 40 is reported. Tetragonal crystals grown in methyl pentanediol belong to space group P4222 with unit-cell parameters a = 94.5, c = 118.3 A. Long thin needles grown from PEG belong to space group C2 with unit-cell parameters a = 125.71, b = 47.3, c = 74.6 A, beta = 93.90 degrees. The N-terminal 170 amino acids have significant homology with the well characterized human cyclophilin A. The C-terminal domain is largely made up of three copies of the tetratricopeptide repeat motif thought to be involved in mediating protein-protein interactions. Cyclophilins are frequently found as domains in larger multidomain proteins. To date, only X-ray structures of single-domain cyclophilins have been reported, and this work provides the first example of the purification and crystallization of a larger protein containing a cyclophilin domain.

Amino Acid Sequence↗
PubMed1997

Immunodetection of PrPSc in spleens of some scrapie-infected sheep but not BSE-infected cows.

The development of diagnostic tools for transmissible spongiform encephalopathies (TSEs) would greatly assist their study and may provide assistance in controlling the disease. The detection of an abnormal form of the host protein PrP in noncentral nervous system tissues may form the basis for diagnosis of TSEs. Using a new antibody reagent to PrP produced in chickens, PrP can be readily detected in crude tissue extracts. PrP from uninfected spleen had a lower molecular mass range than PrP from brain, suggesting a lower degree of glycosylation. A simple method for detecting the abnormal form of the protein, PrPSc, in ruminant brain and spleen has been developed. PrPSc was detected in sheep spleen extracts from a flock affected by natural scrapie and was also found in spleens from some, but not all, experimental TSE cases. In spleens from cattle with bovine spongiform encephalopathy (BSE) no PrPSc was detected. It is therefore suggested that there is differential targeting of PrPSc deposition between organs in these different types of TSE infection which, with other factors, depends on strain of infecting agent.

Animals↗
PubMed1997

The effect of transmission bandwidth on diagnostic accuracy in remote fetal ultrasound scanning.

Six subspecialists with considerable experience in fetal ultrasound viewed a selection of pre-recorded ultrasound scans. Scans from 18 patients recorded on VHS video-tape were supplied from five centres in the UK and Ireland, each made on a high-resolution ultrasound machine by an experienced sonologist at a referral centre. Each observer viewed the scans on a large display monitor in an individual viewing booth. The scans were viewed in random order, at randomly selected bandwidths. Observers, who were blinded to both recording and bandwidth, assessed the technical quality on a five-point Likert scale. They also recorded their diagnosis. The six observers each carried out 32 viewing sessions, which gave a total of 192 viewings. There was no significant difference in the perceived technical quality of the scans between the two bandwidths used (P = 0.09). Of the 84 recordings transmitted at 1920 kbit/s, 71 (85%) were diagnosed correctly or 'half correctly' and 13 (15%) were misdiagnosed. Of the 95 recordings transmitted at 384 kbit/s, 66 (69%) were diagnosed correctly or 'half correctly' and 29 (31%) were misdiagnosed. This difference was significant (P = 0.03). The results indicate that although there were no perceived differences in technical quality between recordings transmitted at 384 or 1920 kbit/s, diagnostic accuracy was marginally worse at the lower bandwidth. This suggests that the higher bandwidth conveys more detail and information to the observer, which in turn enables more accurate diagnosis. However, further work is required before a definitive choice can be made about the optimum transmission bandwidth for remote fetal ultrasound studies.

Female↗
PubMed1996

Protease-resistant PrP deposition in brain and non-central nervous system tissues of a murine model of bovine spongiform encephalopathy.

Infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (BSE) from affected cattle to inbred laboratory mice. Sedimentable, protease-resistant PrP (PrPSc) has also been extracted from BSE-affected cattle brain. Both infectivity and PrPSc have been reported in the lymphoreticular tissues of sheep and mice clinically and preclinically affected with scrapie. Neither infectivity nor PrPSc has yet been detected in non-neural tissues of naturally occurring, clinical cases of BSE in cattle. We have used a murine model of BSE (301V isolate in VM/Dk mice) to investigate when and where PrPSc accumulates. PrPSc was detected both in brain and in extraneural sites prior to the onset of clinical symptoms. This murine BSE model differs, however, in four important aspects from our previously published findings for murine scrapie models: (a) PrPSc was found relatively late into the incubation period; (b) after intracerebral inoculation, PrPSc was found in brain before it was found in other tissues; (c) no PrPSc was found in most of the spleens from clinically affected animals after intracerebral inoculation; and (d) even after intraperitoneal infection, PrPSc was detected in brain first.

Animals↗
PubMed1996

Neutralizing and enhancing activities of human respiratory syncytial virus-specific antibodies.

The neutralizing and enhancing activities of respiratory syncytial virus (RSV)-specific antibodies were examined. These two biological activities were measured for a panel of six monoclonal antibodies (MAbs) specific to the RSV surface F and G glycoproteins. Four MAbs specific for the F protein possessed both neutralizing and enhancing activities. One MAb (11-2-D2), specific to the G protein, enhanced RSV infection of U937 cells, a human macrophage cell line, but did not neutralize virus infectivity. One MAb (11-3-A3), specific to the F protein, efficiently neutralized virus infectivity but did not enhance RSV infection of U937 cells. MAb 11-3-A3 neutralized representative strains of the two antigenic subtypes of RSV. Assays performed with mixtures of MAbs showed that high concentrations of MAb 11-3-A3 masked the enhancing activity of MAb 11-2-D2. The assay of mixtures of two MAbs possessing only enhancing activities demonstrated that this response was synergistic. The role of neutralizing and enhancing antibodies in determining the outcome of RSV infection was examined for infants from whom cord blood serum samples were collected at birth. There was no significant difference in the magnitude of the serum-enhancing activities between infants who were hospitalized with RSV infections and a group of age- and sex-matched control infants with no reported respiratory illness requiring hospitalization. However, the results indicated a possible correlation between RSV infection of the infants and the occurrence of in vitro antibody-dependent enhancement of the cord blood sera at a serum dilution of 10(-2). A significant inverse correlation was found between the plaque-neutralizing and enhancing activities of the cord blood sera from infants, irrespective of subsequent RSV infection. These data are discussed in relation to the possible contribution of antibody-dependent enhancement to the normal course of RSV pathology in vivo.

Antibodies, Monoclonal↗
PubMed1995

Traumatic brain injury: factors predicting return to work or school.

Prediction of outcome for brain-injured individuals will facilitate effective rehabilitation programme planning which will ultimately improve the patient's quality of life. A sample of traumatic brain-injured subjects who had completed their rehabilitation were contacted post-discharge to identify predictive factors for return to work/school. Subjects were given a telephone interview and their charts were examined retrospectively along five subsets of variables in the predictive matrix: sociodemographics, chronicity, indices of severity, physical impairment, and cognitive functioning. Forty-five subjects were used as the study sample to investigate their vocational and educational outcome, and to generate the best predictive model for return to work/school. Twenty subjects made up the test sample used to evaluate the generalizability of the predictive model. Performance IQ score of the Wechsler Adult Intelligence Scale-Revised emerged as the most significant predictor of return to work/school. Implications of these findings for treatment and rehabilitation are discussed.

Activities of Daily Living↗
PubMed1994

Effect of Sinc genotype, agent isolate and route of infection on the accumulation of protease-resistant PrP in non-central nervous system tissues during the development of murine scrapie.

Mice congenic for the Sinc gene were infected intracerebrally with two scrapie strains, ME7 and 22A. At various times during the incubation period tissues were monitored for the infection-specific form of PrP (PrPSc). PrPSc was found in brain, spleen, lymph nodes, pancreas, submaxillary gland and thymus. After intraperitoneal inoculation PrPSc was found in spleen, lymph nodes, pancreas and submaxillary glands prior to its detection in brain. The kinetics of accumulation of PrPSc in these tissues was dependent on the infecting strain of agent, on the mouse Sinc genotype and on the route of infection. This study supports using the presence of PrPSc as an indicator of infectivity in brain and extraneural tissues and defines some of the parameters which influence when and where PrPSc is first found.

Animals↗
PubMed1993

Evaluation of a program for rehabilitation of osteoporotic patients (PRO): 4-year follow-up. The Bone and Mineral Group of the University of Toronto.

The value of a program for the rehabilitation of osteoporotic patients (PRO) was assessed from a 4-year follow up of 139 patients referred to the program over its initial 2 years of operation. The program consisted of educational seminars, social activities and regular exercise supervision. Patients had annual clinical assessments, and bone mass measurements by neutron activation analysis (reported as CaBI). Fitness was assessed by performance on a treadmill (reported in terms of VO2max, ml/kg/min). Seventy-eight of the 139 patients remained in the program over the 4-year follow-up. This unusually high level of commitment to the program is indicative of the psychological value that patients have derived from it. The effect of the program on the osteoporosis process was inconclusive. Group 2, the 37 patients who obtained the greatest improvement in fitness (VO2max > 6 ml/kg/min), had a significantly greater reduction in back pain than did group 1, the 36 with less significant improvement (VO2max < or = 6 ml/kg/min). The bone mass and incidence of vertebral fractures on entry into the program were not significantly different between the two groups. Group 2 had on average a greater increase in bone mass over the 4 years; mean increases in CaBI, (+/- SD) were 0.09 +/- 0.09 and 0.05 +/- 0.10 for groups 2 and 1 respectively. Group 2 had on average fewer new vertebral fractures (0.08 +/- 0.36 and 0.28 +/- 0.75 for groups 2 and 1 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗