Biomedical subjects

R Bayly

Publications and source records attributed to R Bayly.

12 recordsLinked to original sources

PubMed2000

Role for homodimerization in growth deregulation by E2a fusion proteins.

The oncogenic transcription factor E2a-Pbx1 is expressed in some cases of acute lymphoblastic leukemia as a result of chromosomal translocation 1;19. The early observation that E2a-Pbx1 incorporates transcriptional activation domains from E2a and a DNA-binding homeodomain from Pbx1 inspired a model in which E2a-Pbx1 promotes leukemogenic transformation of lymphoid progenitor cells through transcriptional induction of target genes defined by the Pbx1 portion of the molecule. However, the subsequent demonstration that the only known DNA-binding module on the molecule, the Pbx1 homeodomain, is dispensable for the induction of lymphoblastic lymphoma in transgenic mice called into question the contribution made by the Pbx1 portion. In this study, we have used a domain swap approach coupled with a fibroblast-based focus formation assay to evaluate further the requirement for PBX1-encoded peptide elements in growth deregulation by E2a-Pbx1. No impairment of focus formation was observed when the entire Pbx1 portion was replaced with DNA-binding/dimerization domains derived from yeast transcription factor GAL4 or GCN4. Furthermore, replacement of Pbx1 with tandem FKBP domains that mediate homodimerization in the presence of a synthetic ligand led to striking growth deregulation exclusively in the presence of the dimerizing agent. N-terminal elements encoded by E2A, including the AD1 transcriptional activation domain, were required for dimerization-induced focus formation. We conclude that transcriptional target genes defined by heterologous C-terminal DNA-binding modules are not required in growth deregulation by E2a fusion proteins. We speculate that interactions between N-terminal E2a elements and undefined proteins that could function as components of a transcriptional coactivator complex may be more important.

3T3 Cells↗

PubMed1999

Use of flexible intermediate and intensive care to reduce multiple transfers of patients.

OBJECTIVE: To test an alternative flexible approach to traditional fixed intermediate and intensive care to minimize transfers of patients. METHODS: Patients admitted to a 28-bed nursing unit with intermediate care potential and a 12-bed intensive care unit at a 300-bed teaching community hospital were studied. The group included 524 patients with a discharge diagnosis code for mechanical ventilation. During eight 3-week cycles, 1073 transfers of patients were tabulated. A plan-do-study-act method was used to improve weaning from mechanical ventilation and reduce the number of inappropriate days in intensive care. Admissions and transfers to the 2 units for all patients during the eight 3-week cycles were compared over time. Length of stay and mortality were noted for all patients treated with conventional and noninvasive ventilation. RESULTS: Direct admissions to the flexible intermediate unit increased with no overall change in admissions to the intensive care unit. Fewer patients needed conventional ventilation, and more in both units were treated with noninvasive ventilation. The median number of transfers per patient treated with mechanical ventilation decreased from 1.94 to 1.20. Length of stay and mortality also decreased among such patients. Some cost savings were attributable to the decrease in the number of transfers. Transfers out of the hospital directly from the intensive care unit increased from 2.24% to 4.43%. CONCLUSIONS: In a community teaching hospital, flexible care policies decreased the number of in-hospital transfers of patients treated with mechanical ventilation.

Critical Care↗

PubMed1997

Incidence of deep venous thrombosis associated with femoral venous catheterization.

OBJECTIVE: To determine in adult medical patients the incidence of deep venous thrombosis (DVT) resulting from femoral venous catheterization (FVC). METHODS: A prospective, observational study was performed at a 420-bed community teaching hospital. Heparin-coated 7-FR cm femoral venous catheters were inserted unilaterally into a femoral vein. Each contralateral leg served as a control site. Age, gender, number of FVC days, DVT risk factors, administration of DVT prophylaxis, and DVT formation and site were tabulated for each patient. Venous duplex sonography was performed bilaterally on each patient within 7 days of femoral venous catheter removal. RESULTS: Catheters were placed in 29 men and 13 women. Femoral DVT was identified by venous duplex sonography in 11 (26.2%) of the FVC legs and none (0%) in the control legs. Posterior tibial and popliteal DVT was identified in both the FVC and control legs of 1 patient. DVT formation at the site of FVC insertion was highly significant (p = 0.005). There were no statistically significant associations with age (p = 0.42), gender (p = 0.73), number of DVT risk factors (p = 0.17), number of FVC days (p = 0.89), or DVT prophylaxis (p = 0.99). CONCLUSION: Placement of femoral catheters for central venous access is associated with a significant incidence of femoral DVT as detected by venous duplex sonography criteria at the site of femoral venous catheter placement. Physicians must be aware of this risk when choosing this vascular access route for adult medical patients. Further studies to assess the relative risk for DVT anf its clinical sequelae when using the femoral vs other central venous catheter routes are indicated.

Adult↗

PubMed1994

Clinical features and natural history of Beckwith-Wiedemann syndrome: presentation of 74 new cases.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome with variable expression. To define the range and frequency of complications in BWS, we have studied a cohort of 76 affected patients (two previously reported). The most frequent complications were macroglossia (97%), abdominal wall defect (80%) and birth weight or postnatal growth > 90th centile (88%). Other common features were ear creases/pits (76%), facial naevus flammeus (62%), nephromegaly (59%) and hypoglycaemia (63%). Rarer complications included hemihypertrophy (24%), moderate/severe developmental delay (4%), congenital heart defects (6.5%), polydactyly (4%), neoplasia (4%) and cleft palate (2.5%). Pre-term labour occurred in 53% and polyhydramnios in 33% of BWS pregnancies. The six deaths all occurred in babies born pre-term, three of whom had major congenital abnormalities. Five patients (6.5%) from four kindreds had an unequivocal family history of BWS, but 15 of 68 apparently sporadic cases had a relative with possible BWS (minor features only). Incomplete penetrance may lead to familial BWS being underdiagnosed.

Adolescent↗

PubMed1991

ELISA for identification of blood meal source in black flies (Diptera: Simuliidae).

A modified ELISA, in which a biotinylated second antibody and a streptavidin-biotinylated peroxidase complex are used, has been developed to identify the blood meal sources of black flies. The modified assay is sensitive enough to identify correctly 100% of blood meals at 73 h postingestion and 80% of blood meals at 116 h postingestion in black flies held in the field at ambient temperatures.

Animals↗

PubMed1988

Driving pressure and arterial carbon dioxide tension during high-frequency jet ventilation in postoperative patients.

To achieve normocarbia during conventional mechanical ventilation, ventilator settings are determined initially on the basis of body weight. The best ventilator settings for CO2 elimination during high-frequency jet ventilation (HFJV) have not been so clearly defined. A recent study has suggested that eucarbia will be obtained with HFJV when tidal volume (VT) per kg of body weight is kept within a narrow, well-defined range. In the same study, a "bench test" demonstrated that VT was directly proportional to the jet ventilator driving pressure (DP). The goal of our study was to confirm this recommended VT/kg to obtain eucarbia and to determine whether the relation observed between VT and DP in the laboratory was true clinically. We studied 14 patients admitted to the ICU for postoperative support. We determined a good correlation between DP and VT/kg (r = .811, p less than .001) for the group as a whole and a good inverse correlation between DP or VT/kg and PaCO2 for most individual patients; however, there was a poor inverse correlation between DP or VT/kg and PaCO2 for the group as a whole, due to wide patient-to-patient variation in the efficiency of jet ventilation. We conclude that there is no universal formula for setting jet ventilator DP or VT/kg to affect normocarbia in humans.

Body Weight↗

PubMed1987

Synchronous versus nonsynchronous high-frequency jet ventilation: effects on cardiorespiratory variables and airway pressures in postoperative patients.

In order to compare the differences of high-frequency jet ventilation (HFJV) synchronized with the cardiac cycle (sync) to that nonsynchronized with the cardiac cycle (async), ten stable postoperative ICU patients, without heart failure, in sinus rhythm were ventilated randomly in either mode. The async mode was HFJV at 100 cycle/min, while the sync mode was HFJV triggered by the R-wave of the ECG tracing. The heart rate ranged between 64 and 127 beat/min. Synchronization was studied at one of two periods, sync 0 and sync 60. Sync 0 consisted of inspiration triggered by the R-wave, with jet ventilation occurring early in systole; sync 60 represented a 60% delay of the time between the succeeding R-waves, with jet ventilation occurring in mid-diastole. There was no significant difference in the cardiorespiratory data when async was compared to either sync 0 or sync 60. Therefore, in these patients without heart failure, the selection of async vs. either sync mode appeared to have neither adverse nor beneficial hemodynamic effects.

Evaluation Studies as Topic↗

PubMed1984

Use of monoclonal antibodies to investigate a possible role of thyroglobulin in the pathogenesis of Graves' ophthalmopathy.

One possible mechanism for Graves' ophthalmopathy is that the progressive orbital inflammation is initiated by formation of thyroglobulin (Tg)-anti-Tg immune complexes at sites of Tg binding to extraocular muscle membranes. In this study monoclonal antibodies (MCAB) against human Tg were used as probes (1) to identify Tg in eye muscle membranes prepared from normal subjects and (2) to measure binding of human Tg and Tg-anti-Tg immune complexes to eye muscle membranes. Reactivity of anti-Tg MCAB with Tg, thyroid, and eye muscle membranes was determined by binding of [125I]anti-Tg monoclonal antibody, an enzyme-linked immunosorbent assay (ELISA), and the indirect immunofluorescence technique. Seven membrane fractions, prepared by differential sucrose gradient centrifugation, were used. Whereas [125I]anti-Tg MCAB bound to all thyroid membrane fractions tested, no [125I]anti-Tg bound to eye muscle membranes. Similarly, reactivity of anti-Tg MCAB with eye muscle membranes was not demonstrated in ELISA or immunofluorescence tests. Although Tg-anti-Tg immune complexes bound to thyroid membranes, such complexes did not bind to eye muscle membranes. Significant binding of [125I]human Tg to eye muscle or thyroid membranes was not demonstrated for any membrane preparation. On the other hand moderate, but significant, binding to skeletal muscle was shown. Similar results were found using an ELISA. Binding of [125I]anti-Tg-Tg complexes of [125I]Tg to thyroid and eye muscle membranes was not affected by the presence of normal human serum, phosphate ions, pH, or incubation temperature, conditions claimed by others to be critical for Tg and Tg-anti-Tg immune complex binding. Since Tg is not present in normal human eye muscle a major role of Tg, or Tg-anti-Tg immune complexes, in the pathogenesis of Graves' ophthalmopathy appears to have been excluded by these findings.

Animals↗

PubMed1982

Demonstration of a circulating autoantibody against a soluble eye-muscle antigen in Graves' ophthalmopathy.

Mouse monoclonal antibodies against antigens in human eye muscle, orbital connective tissue, and lacrimal tissue and guineapig harderian gland have been produced by means of the hybridisation technique. From 14 fusions, over 30 antibodies have been produced, of which 24 have been maintained and characterised for the present studies. All were IgG1. Most were organ-specific, but eye-muscle antibodies tended to cross-react with skeletal muscle, one eye-muscle antibody cross-reacted with thyroidal microsomes, and both lacrimal monoclonal antibodies reacted strongly with mucus-secreting cells in human small intestine. Only one of the antibodies fixed complement. Orbital monoclonal antibodies were used as probes to identify orbital antigens. Most antigens were in the cytosol fraction, but a few were demonstrated in cytoplasmic membranes. Circulating autoantibodies against a human-eye-muscle soluble antigen were detected in 17 of 23 patients with Graves' ophthalmopathy but in only 1 of 14 patients with Hashimoto's thyroiditis, in 2 of 11 patients with subacute thyroiditis, in no patient with Graves' hyperthyroidism without eye disease, and in none with multinodular goitre.

Adolescent↗

PubMed1982

Thyroid-stimulating hormone (TSH) receptor antibodies and antibodies stimulating adenyl cyclase in relatives from two families with a high prevalence of Graves' hyperthyroidism: a ten-year follow-up study.

Thyroid-stimulating hormone (TSH) receptor antibodies and antibodies stimulating adenyl cyclase were measured in 47 relatives of patients with Graves' hyperthyroidism from two families with a high prevalence of the disease, in whom bioassays for the long-acting thyroid stimulator (LATS) had been performed 10 years earlier. Tests were also carried out in six propositi from the two families and age- and sex-matched normal subjects from six families. There had been no new cases of hyperthyroidism since the first study, although one subject was clinically and biochemically hyperthyroid at the time of study and two more were biochemically borderline hyperthyroid but clinically euthyroid. Levels of serum T4 thyrotropin, and percentage T3 resin uptake and free thyroxine indices were similar for relatives and normal subjects, although the mean serum T3 level for relatives was significantly greater than that for the normal subjects. Antibodies were not detected by either assay in any relative. Significant titers of antithyroglobulin antibodies were demonstrated in 4 of 44 relatives but in none of 46 normals tested, while thyroid cytoplasmic antibodies were detected in 8 of 44 relatives and 3 of 45 normals. The mean serum IgG for Graves' relatives was significantly greater than that for the normals, although the mean IgM and IgA levels for the two groups were not significantly different.

Adenylyl Cyclases↗

PubMed1982

Broad-host-range IncP-4 plasmid R1162: effects of deletions and insertions on plasmid maintenance and host range.

R1162 is an 8.7-kilobase (kb) broad-host-range replicon encoding resistance to streptomycin and sulfa drugs. In vitro deletion of 1.8-kb DNA between coordinates 3.0 and 5.3 kb did not affect plasmid maintenance, but a Tn1 insertion at coordinate 6.3 kb led to a recessive defect in plasmid maintenance. The only cis-acting region necessary for plasmid replication appears to lie between the Tn1 insertion at coordinate 6.3 kb and a second Tn1 insertion at coordinate 6.5 kb. All R1162 sequences between position 6.5 kb and the EcoRI site at coordinate 8.7/0 kb were dispensible for replication in Escherichia coli and Pseudomonas putida. Plasmids carrying insertions in a variety of restriction sites in an R1162::Tn1 derivative were unstable in P. putida but stable in E. coli. Tn5 insertions in R1162 showed a hot spot at coordinate 7.5 kb. A Tn5 insertion at coordinate 8.2 kb appeared to mark the 3' end of the streptomycin phosphotransferase coding sequence. All R1162::Tn5 derivatives showed specific instability in Pseudomonas strains but not in E. coli. The instability could be relieved by internal deletions of Tn5 sequences. In the haloaromatic-degrading Pseudomonas sp. strain B13, introduction of an unstable R1162::Tn5 plasmid led to loss of ability to utilize m-chlorobenzoate as a growth substrate. Our results showed that alteration of plasmid sequence organization in nonessential regions can result in restriction of plasmid host range.

Base Sequence↗

PubMed1982

Nature of thyrotropin displacement activity in subacute thyroiditis.

Using a radioreceptor assay and serum immunoglobulin (Ig) prepared by ammonium sulfate precipitation, significant TSH displacement activity (TDA) was demonstrated in 5 of 15 patients with subacute thyroiditis tested during the acute phase. Using a cAMP generation assay, adenyl cyclase stimulation by Ig from patients with subacute thyroiditis was not demonstrated. The nature of the TDA demonstrated in subacute thyroiditis was investigated to determine whether the factor measured was TSH receptor antibody, as is found in Graves' hyperthyroidism, or thyroglobulin, which is know to give false positive responses in the radioreceptor assay. When Ig was prepared by DEAE+-Sephadex chromatography, mean TSH displacement indices were similar to those given by ammonium sulfate-prepared Ig for both Graves' disease and subacute thyroiditis. On the other hand, when Ig was prepared by DEAE+-cellulose chromatography, which isolates highly purified IgG, mean indices were significantly less than for ammonium sulfate-prepared Ig for both Graves' hyperthyroidism and subacute thyroiditis. Thyroglobulin was not detected in Ig prepared by any of the 3 methods. Although high concentrations of crude thyroid-soluble fraction and purified thyroglobulin gave strongly positive responses in the radioreceptor assay, concentrations of thyroglobulin over the range found in the sera of patients with subacute thyroiditis could not be shown to give positive responses. Moreover, TSH displacement indices did not correlate with serum thyroglobulin levels. As determined by species cross-reactivity and dose-responses studies, the TDAs demonstrated in subacute thyroiditis and Graves' hyperthyroidism were similar. It was concluded that the TDA demonstrated in subacute thyroiditis represents antibody which binds to, but does not stimulate, the TSH receptor.

Adolescent↗