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Biomedical subjects

M E Ward

Publications and source records attributed to M E Ward.

At least 91 records · Page 5Linked to original sources
PubMed1992

Multidomain binding of transforming growth factor alpha to the epidermal growth factor receptor.

Solubilized epidermal growth factor receptor (EGF-R) has been used in an extension of the Geysen epitope mapping protocol in order to provide additional insight into the amino acid residues in human transforming growth factor alpha (hTGF alpha) which are critical to recognition and binding. Overlapping heptapeptides which encompassed the 50 amino acid primary sequence of hTGF alpha were synthesized on a polyethylene solid phase, and the amount of detergent-solubilized EGF-R bound to each peptide was measured using ELISA. EGF-R appeared to bind reproducibly to four heptapeptides cognate to sequences in both the N- and C-domains of hTGF alpha (residues 22-28, 28-34, 36-42, and 44-50). Visualization of these four regions on three-dimensional solution phase structures of hTGF alpha, derived from 1H NMR measurements [Kline, T.-P., Brown, F.K., Brown, S.C., Jeffs, P.W., Kopple, K.D., & Mueller, L. (1990) Biochemistry 29, 7805-7813], indicated that the peptide segments are located on a single face of the protein and suggested the presence of a potential receptor binding cavity. If peptide segments within both the N- and C-domains of hTGF alpha are involved in binding to EGF-R, then this has direct consequences for possible molecular mechanisms by which receptor activation might take place. For example, the observed conformational flexibility in the six NMR-derived hTGF alpha structures due to variations in the main-chain torsion angles of Val-33, in combination with the involvement of residues from both domains in the proposed binding cavity, may imply that receptor activation results from interdomain reorientation in the protein ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Survey of 3765 cardiopulmonary resuscitations in British hospitals (the BRESUS Study): methods and overall results.

OBJECTIVE: To determine the circumstances, incidence, and outcome of cardiopulmonary resuscitation in British hospitals. DESIGN: Hospitals registered all cardiopulmonary resuscitation attempts for 12 months or longer and followed survival to one year. SETTING: 12 metropolitan, provincial, teaching, and non-teaching hospitals across Britain. SUBJECTS: 3765 patients in whom a resuscitation attempt was performed, including 927 in whom the onset of arrest was outside the hospital. MAIN OUTCOME MEASURE: Survival after initial resuscitation, at 24 hours, at discharge from hospital, and at one year, calculated by the life table method. RESULTS: There were 417 known survivors at one year, with 214 lost to follow up. By life table analysis for every eight attempted resuscitations there were three immediate survivors, two at 24 hours, 1.5 leaving hospital alive, and one alive at one year. Survival at one year was 12.5% including out of hospital cases and 15.0% not including these cases. Each hospital year averaged 30 survivors at one year: three who had an arrest outside hospital, seven who had one in the accident and emergency department, seven in the cardiac care unit, 10 in the general wards, and three in other, non-ward areas. Within the hospitals survival rates were best in those who had an arrest in the accident and emergency department, the cardiac care unit, or other specialised units. Outcome varied 12-fold in subgroups defined by age, type of arrest, and place of arrest. CONCLUSION: 71% of the mortality at one year in patients undergoing attempted resuscitation occurred during the initial arrest. Hospital resuscitation is life saving and cost effective and warrants appropriate attention, training, coordination, and equipment.

Age Factors↗
PubMed1992

A longitudinal study of trachoma in a Gambian village: implications concerning the pathogenesis of chlamydial infection.

In order to investigate risk factors for the acquisition of trachoma, and to study the effect of continued exposure to ocular chlamydial infection on the severity of inflammatory trachoma and its cicatricial sequelae, a longitudinal study was conducted in a Gambian village. Over a 20-month period, the incidence of active (inflammatory) trachoma was significantly higher among those sharing a bedroom with an active case (64/561, 11.4%) than among those who were not exposed in this way (37/658, 5.6%) (relative risk 1.97, 95% confidence interval 1.33-2.90). There was a positive trend in the odds ratio for severe to moderate inflammatory disease versus mild disease as the number of active cases in the bedroom increased, but this failed to achieve statistical significance (P = 0.0506). Individuals with inflammatory trachoma of moderate or severe intensity at one survey were significantly more likely than others to have moderate or severe inflammatory changes at a previous or subsequent survey (odds ratio 14.9, 95% confidence interval 3.9-68.0), implying that host factors may be more important determinants of severity than the frequency of exposure to reinfection.

Adolescent↗
PubMed1992

Genotyping of Chlamydia trachomatis from a trachoma-endemic village in the Gambia by a nested polymerase chain reaction: identification of strain variants.

Direct amplification of the major outer membrane protein (MOMP) gene by polymerase chain reaction (PCR) was used to identify Chlamydia trachomatis in eye swabs from clinically active cases of endemic trachoma in a Gambian village. Chlamydial DNA was detected in 51% of 96 subjects with clinically active disease and in 5% of 37 clinically negative individuals. The PCR detection was combined with typing, using nested primers to variable sequences (VS) 1, 2, and 4 of the MOMP genes to distinguish between trachoma genotypes A, B, and C, respectively. Genotypes A and B were detected in the village, with some individuals harboring both genotypes within the same eye. DNA sequencing revealed strain variants of both genotypes. Typing of genotype and strain variants is now in progress to study trachoma transmission within the village.

Bacterial Outer Membrane Proteins↗
PubMed1992

Quantitative assessment of bed rise difficulty in young and elderly women.

OBJECTIVE: To describe the motions which occur during rising from bed, specifically the motions that appeared to characterize difficulty in rising from a bed in older adults. DESIGN: Development of a Mobility assessment tool. SETTING: Retirement center and two university laboratories. PARTICIPANTS: Three groups of female volunteers: young controls (n = 17, mean age 24), community-dwelling older adults (n = 12, mean age 71), and retirement center-dwelling older adults who admitted to difficulty in rising from a bed (n = 15, mean age 86). INTERVENTION: Videotaping of motions occurring during controlled rises from a supine to sitting position. MAIN OUTCOME MEASURES: These motions were rated on the specially developed Bed Rise Difficulty (BRD) scale, a scale designed to measure movements that characterize difficulty in rising from a bed in older adults. Subject groups were compared in total BRD score, individual BRD item score, and total time to rise. Item relationships and scale reliability were also assessed. RESULTS: Older adults with no apparent difficulty in rising based on total time to rise or on the BRD score nevertheless showed differences in upper extremity use when compared to young controls. Older adult subjects with difficulty in rising from a bed, when compared to other older adults with no apparent difficulty, differed more often in their upper extremity and leg use to facilitate the rise. Five BRD scale items, including use of extremity pushes, discontinuity of trunk and leg motion, multiple shoulder/pelvic adjustments, multiple leg adjustments, and poor vertical heel clearance may have best indicated true bed rise difficulty. CONCLUSIONS: These data provide a reliable and valid method to characterize difficulty in rising from a bed and provide the basis for biomechanical analyses of the strength and joint ranges of motion required to rise from a bed.

Activities of Daily Living↗
PubMed1992

Analysis of human chest wall motion using a two-compartment rib cage model.

We present a model of chest wall mechanics that extends the model described previously by Macklem et al. (J. Appl. Physiol. 55: 547-557, 1983) and incorporates a two-compartment rib cage. We divide the rib cage into that apposed to the lung (RCpul) and that apposed to the diaphragm (RCab). We apply this model to determine rib cage distortability, the mechanical coupling between RCpul and RCab, the contribution of the rib cage muscles to the pressure change during spontaneous inspiration (Prcm), and the insertional component of transdiaphragmatic pressure in humans. We define distortability as the relationship between distortion and transdiaphragmatic pressure (Pdi) and mechanical coupling as the relationship between rib cage distortion and the pressure acting to restore the rib cage to its relaxed configuration (Plink), as assessed during bilateral transcutaneous phrenic nerve stimulation. Prcm was calculated at end inspiration as the component of the pressure displacing RCpul not accounted for by Plink or pleural pressure. Prcm and Plink were approximately equal during quiet breathing, contributing 3.7 and 3.3 cmH2O on average during breaths associated with a change in Pdi of 3.9 cmH2O. The insertional component of Pdi was measured as the pressure acting on RCab not accounted for by the change in abdominal pressure during an inspiration without rib cage distortion and was 40 +/- 12% (SD) of total Pdi. We conclude that there is substantial resistance of the human rib cage to distortion, that, along with rib cage muscles, contributes importantly to the fall in pleural pressure over the costal surface of the lung.

Adult↗
PubMed1992

Effect of phrenic afferent stimulation on pattern of respiratory muscle activation.

Ventilation and electromyogram (EMG) activities of the right hemidiaphragm, parasternal intercostal, triangularis sterni, transversus abdominis, genioglossus, and alae nasi muscles were measured before and during central stimulation of the left thoracic phrenic nerve in 10 alpha-chloralose anesthetized vagotomized dogs. Pressure in the carotid sinuses was fixed to maintain baroreflex activity constant. The nerve was stimulated for 1 min with a frequency of 40 Hz and stimulus duration of 1 ms at voltages of 5, 10, 20, and 30 times twitch threshold (TT). At five times TT, no change in ventilation or EMG activity occurred. At 10 times TT, neither tidal volume nor breathing frequency increased sufficiently to reach statistical significance, although the change in their product (minute ventilation) was significant (P less than 0.05). At 20 and 30 times TT, increases in both breathing frequency and tidal volume were significant. At these stimulus intensities, the increases in ventilation were accompanied by approximately equal increases in the activity of the diaphragm, parasternal, and alae nasi muscles. The increase in genioglossus activity was much greater than that of the other inspiratory muscles. Phrenic nerve stimulation also elicited inhomogeneous activation of the expiratory muscles. The transversus abdominis activity increased significantly at intensities from 10 to 30 times TT, whereas the activity of the triangularis sterni remained unchanged. The high stimulation intensities required suggest that the activation of afferent fiber groups III and IV is involved in the response. We conclude that thin-fiber phrenic afferent activation exerts a nonuniform effect on the upper airway, rib cage, and abdominal muscles and may play a role in the control of respiratory muscle recruitment.

Animals↗
PubMed1992

Oxygen delivery-independent effect of blood flow on diaphragm fatigue.

To determine the effect of blood flow on diaphragm fatigue independent of oxygen delivery, the left hemidiaphragm was vascularly isolated in 14 pentobarbital-anesthetized, mechanically ventilated dogs. Fatigue (decline in tension generation) of the left diaphragm was induced by phrenic nerve stimulation at 10 Hz, 12/min, duty cycle of 0.5 for 8 min. Two stimulation periods separated by 30 min of rest were performed in each animal. Diaphragmatic O2 delivery during the two periods was the same. In Group 1 (n = 8), the diaphragm was autoperfused from the femoral artery (high O2-low flow) during the first stimulation period. The tension generated by the diaphragm during this period declined progressively to 47.7% of initial values. In the second period in this group, the diaphragm was pump perfused with arterial blood, diluted with an equal volume of 6% dextran at a flow rate twice that of the first period (low O2-high flow). Tension in this period declined to 76% of initial tension (p less than 0.05 compared with high O2-low flow). In Group 2 (n = 6), stimulation performed while perfusing the diaphragm in the first period with diluted arterial blood at a flow rate twice that recorded during autoperfusion (low O2-high flow) produced a decline in tension to 70% of the initial values. In the second period, the diaphragm was perfused with undiluted arterial blood at a flow rate equal to 50% of that of the first period (high O2-low flow). Tension during this period declined to 56% of initial values (p less than 0.05 compared with low O2-high flow).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Vector analysis in partitioning of inspiratory muscle action in dogs.

We considered the displacements and the pressure changes resulting from isolated contraction of 2 muscles as analogous to 2 vectors and those during simultaneous contraction as resultants. These were resolved into contributing components to calculate the contribution of each muscle group and partition the action of inspiratory muscles. Relative displacements of rib cage (delta RC) and abdomen (delta AB) and changes in transpulmonary (delta PL) and abdominal (delta Pab) pressures were obtained during spontaneous breathing, isolated contraction of rib cage muscle (RCM), diaphragmatic (DI), costal and crural diaphragm and passive inflation in 7 dogs. The diaphragm accounted for 58 +/- 19.8% SD of the chest wall displacement and 90 +/- 6.6% SD of the pressure swings during spontaneous breathing. The costal diaphragm accounted for 61 +/- 28.9% SD of the displacement produced by contraction of the entire diaphragm. Despite wide variability in the action of the diaphragm and its components, all animals breathed close to their relaxation characteristic. We conclude that there are marked differences in the degree of RCM recruitment between dogs in order to prevent chest wall distortions.

Animals↗
PubMed1991

Hemodynamic effects of lobar pulmonary artery occlusion in a porcine sepsis model.

We induced severe pulmonary hypertension and acute lung injury in 6 pigs by Pseudomonas aeruginosa infusion. We studied the effect of pulmonary artery catheter inflation of a pulmonary artery catheter balloon in the left lower lobar pulmonary artery was accompanied by a significant (p less than 0.05, paired t test) increase in pulmonary artery pressure, a decrease in left atrial pressure, a decrease in cardiac output, and a decrease in mean arterial pressure. No significant changes occurred when the catheter was advanced into the wedged position without balloon inflation. Balloon inflation had no significant effect on these variables before bacterial infusion. We conclude that with sufficiently severe pulmonary hypertension in association with diffuse lung injury, lobar pulmonary artery occlusion may cause alterations in cardiac output and left atrial pressure. This may confuse interpretation of pulmonary artery catheter measurements.

Animals↗
PubMed1991

Respiratory muscle activation by limb muscle afferent stimulation in anesthetized dogs.

In 10 chloralose anaesthetized and spontaneously breathing dogs, we assessed the effect of limb muscle afferents on the peak integrated EMG activities of the genioglossus, alae nasi, costal diaphragm, parasternal intercostal, triangularis sterni, and transverse abdominis muscles. The influence of vagal and baroreceptor afferents were eliminated by vagotomy and perfusion of carotid sinuses at a constant pressure. Muscle afferents were activated by stimulating the central end of the gastrocnemius nerve for 1 min at 40 Hz and at different voltages. Stimulation at voltages equal to 5, 10 and 20 times twitch-threshold increased minute ventilation to 165, 216 and 250% of pre-stimulation values, respectively, which was achieved by increasing breathing frequency (shortening of the inspiratory and expiratory times) and tidal volume. The activity of the parasternal intercostal and alae nasi muscles increased by a similar degree to that of the diaphragm while the activities of the genioglossus and transverse abdominis were augmented to a greater degree than that of the diaphragm. On the other hand, the motor drive to triangularis sterni increased significantly only at 20 times twitch-threshold and to a lesser degree than that to the diaphragm. These results suggest that upper airway, inspiratory and expiratory rib cage and abdominal muscles may be independently regulated. Differences in the sensitivity of these muscles to the activation of limb muscle afferents can be explained by a complex pattern of central projections of these afferents on the central respiratory controllers or by intrinsic properties of the motor output of these controllers.

Animals↗
PubMed1991

Nucleotide sequence and taxonomic value of the major outer membrane protein gene of Chlamydia pneumoniae IOL-207.

Chlamydia pneumoniae IOL-207 genomic DNA was hybridized with a 1.5 kb labelled DNA probe containing the 3' region of the coding sequence for the major outer membrane protein (MOMP) of C. trachomatis serovar L1. An 8.5 kb Bg/II fragment containing the complete MOMP gene was cloned into lambda EMBL3. Two hybridizing EcoRI fragments were sub-cloned into the lambda ZAP II cloning vector and the resulting plasmids were used as templates for sequencing both strands of the C. pneumoniae MOMP gene. Computer taxonomic studies using the nucleotide and inferred amino acid sequence of the MOMP of C. pneumoniae IOL-207 and all known chlamydial MOMP sequences supported the designation of C. pneumoniae as a new species, but electron microscope studies suggested that the presence of pear-shaped elementary bodies (EBs) may not be a reliable taxonomic criterion.

Amino Acid Sequence↗
PubMed1991

Chlamydia trachomatis major outer membrane protein epitopes expressed as fusions with LamB in an attenuated aro A strain of Salmonella typhimurium; their application as potential immunogens.

The major outer-membrane protein (MOMP) of Chlamydia trachomatis is the focus of attention for chlamydial vaccine design, particularly those serovar- and subspecies-specific epitopes which provoke neutralizing immune responses. Selected surface-exposed B-cell epitopes of MOMP, incorporating B-subspecies specificities, were expressed as fusions with LamB, an inducible outer-membrane transport protein of Escherichia coli. These recombinant chlamydial-LamB proteins were correctly transported to the outer membrane of both E. coli and an aro A mutant of Salmonella typhimurium. The immunogenicity of the constructs was investigated in a mouse model of chlamydial salpingitis. After oral immunization, recombinant S. typhimurium were recovered from the livers of mice for up to two weeks, and a serum IgG response was induced both to the Salmonella and to the inserted chlamydial epitopes. By contrast, intravenous inoculation was ineffective. Although these LamB fusions proved only weakly immunogenic, this approach should be useful for investigating the ability of attenuated S. typhimurium vaccines incorporating chlamydial epitopes to stimulate protective mucosal immunity in the mouse model of chlamydial salpingitis.

Administration, Oral↗
PubMed1991

The role of Chlamydia trachomatis and Neisseria gonorrhoeae in the aetiology of ectopic pregnancy in Gabon.

OBJECTIVE: To study the association between ectopic pregnancy and Chlamydia trachomatis and Neisseria gonorrhoeae. DESIGN: A prospective observational study with two comparison groups. SETTING: A general hospital in Franceville, Gabon. SUBJECTS: Forty-five women with ectopic pregnancies and two comparison groups each of 45 women, one at 5 to 12 and the other at 32 to 41 weeks gestation. MAIN OUTCOME MEASURES: Serum levels of IgG and IgA antibodies to C. trachomatis (L1 and rMOMP) and N. gonorrhoeae (pili) in all the women. In the women with ectopic pregnancy peritoneal adhesions were scored and in 40 women samples of tube were cultured for organisms being studied. RESULTS: IgG and IgA antibodies to C. trachomatis (L1) were detected in 84% of the ectopic group and 53 and 39% of the comparison groups (P less than 0.0001). IgG and IgA antibodies to N. gonorrhoeae occurred in 49, 28 and 18% and 49, 28 and 26% of the groups but the differences were not statistically significant. Adhesions were positively associated with the antibodies. C. trachomatis was cultured from the tubes of 71% of the women with ectopic pregnancy. CONCLUSIONS: Infection with chlamydia, and probably with N. gonorrhoeae, is an important factor in the causation of ectopic pregnancy in Gabon.

Antibodies, Bacterial↗