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Biomedical subjects

C Bailey

Publications and source records attributed to C Bailey.

At least 19 recordsLinked to original sources

Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in first remission: experience in MRC UKALL X.

Bone marrow transplantation (BMT) has been recommended for children with high-risk acute lymphoblastic leukaemia (ALL) in first remission. The recent MRC UKALL X trial was designed to facilitate a non-randomised comparison between BMT and chemotherapy in children deemed to be at high risk of treatment failure. 198 children aged 1-15 had a presenting leucocyte count of more than 100 x 10(9)/l. All received induction and early intensification therapy. Children with an HLA-compatible sibling donor were eligible for BMT in first remission. All other children received cranial irradiation at 24Gy, late intensification, and two years of continuous treatment. 183 children achieved a stable remission of whom 111 were HLA typed; these tended to be older and to have T-cell ALL. A donor was identified in 41 cases, of whom 34 proceeded to BMT at a median time of 17 weeks; there was no difference in distribution of age, sex, or leucocyte count between the groups receiving BMT and chemotherapy. Comparison of the 144 children who were in remission at 17 weeks and received chemotherapy with the 34 proceeding to BMT showed no significant difference in event-free survival at five years (69% for BMT and 52% for chemotherapy). There were significantly more treatment-related deaths in the marrow transplant group (6 vs 4) and more relapses in the chemotherapy group (59 vs 4). There was no significant difference in event-free survival between children who were HLA typed and had a donor and those without a donor, although there were fewer relapses among the former. BMT can be evaluated in the context of a multicentre trial for paediatric ALL but the number of children with donors is too small to make a significant impact on overall survival. However, marrow transplantation was associated with a much lower relapse rate than that with the UK ALL protocol, and with better definition of higher risk patients BMT may be of benefit in some children with high-risk ALL in first remission.

Adolescent

Purification and identification of bovine liver gamma-carboxylase.

The microsomal gamma-carboxylase catalyzes modification of a limited set of glutamyl residues to gamma-carboxyglutamyl residues in a vitamin K-dependent reaction that also utilizes O2 and CO2. We report the purification to apparent homogeneity of the bovine liver microsomal carboxylase. Affinity chromatography exploiting the association of the carboxylase with prothrombin precursor and carboxylase binding to the propeptide sequence were combined with ion-exchange chromatography and fractionation using immobilized lectins. A 3.5 x 10(5)-fold purification was obtained, which is the highest purification, by a factor of 35, yet reported for this enzyme. A single 98-kDa protein is obtained from this isolation. Carboxylase activity is associated with this protein by two different criteria. Antibodies prepared against the carboxylase detected the 98-kDa protein when used in Western analysis. In addition, the single 98-kDa protein was shown to comigrate with activity when electrophoresed in a nondenaturing gel system. The availability of purified preparations of carboxylase will facilitate an increased understanding of the complex biochemical reaction carried out by this protein.

Animals

Cation-dependent transition between the quadruplex and Watson-Crick hairpin forms of d(CGCG3GCG).

The DNA oligonucleotide d(CGCG3GCG) can form either a Watson-Crick (WC) hairpin or a parallel-stranded quadruplex structure containing six G-quartet base pair assemblies. The exchange between these forms and single strands can be monitored using circular dichroism (CD). NMR results verified the assignment of specific CD bands to quadruplex and hairpin species, respectively. Cations stabilize the quadruplex in the order K+ greater than Ca2+ greater than Na+ greater than Mg2+ greater than Li+ and K+ greater than Rb+ greater than Cs+, indicating that K+ has an optimum ionic radius for complex formation and that ionic charge affects the extent of ion-induced stabilization. The quadruplex is stable in the presence of 40 mM K+ at micromolar DNA concentration and can be kinetically trapped as a metastable form when prepared at millimolar DNA concentration and then diluted into buffer containing 40 mM Na+. The concentration of K+ required to reverse the equilibrium from the hairpin to the quadruplex decreases sharply with increased DNA concentration. The quadruplex has an unusual pKa of ca. 6.8, indicating that C.C+ base pairs are probably forming. This system provides insights into some of the detailed structural characteristics of a ["G4-DNA".ion] complex and an experimental model for the recently proposed "sodium-potassium conformational switch" [Sen, D., & Gilbert, W. (1988) Nature 334, 364-366; Sen, D., & Gilbert, W. (1990) Nature 344, 410-414]. These results may help to explain the lack of cytidine residues in G-rich telomeric DNAs and suggest that methylation of GC-rich duplex DNAs in "GpC islands" may induce quadruplex formation within heterochromatin domains, resulting in reversible chromosomal condensation.

Base Sequence

Intrapartum fetal stimulation testing.

Intrapartum vibroacoustic stimulation testing (VAST) had a sensitivity of 100%, a specificity of 59.6% and a positive predictive value of 27.6% for the detection of fetal acidosis in this study of 60 cases. The use of VAST could significantly reduce the requirement for fetal capillary blood sampling. However, fetal scalp stimulation (FSS) was found to be an unreliable test to exclude fetal acidosis.

Acidosis

Measurement of dopamine, HVA and HMMA in untimed urine samples: establishment of age-related reference data in children.

We describe assays for homovanillic acid, hydroxymethylmandelic acid and dopamine that have proven practical and reliable during 3 years of routine use. Homovanillic and hydroxymethylmandelic acids were measured as trimethyl silyl derivatives by capillary gas chromatography. Dilution of samples prior to extraction was found to be necessary to achieve consistent recoveries of these acidic metabolites. Dopamine was assayed by high pressure liquid chromatography with electrochemical detection using an optimized method of catecholamine isolation that involved both ion exchange and alumina extraction. Untimed urine samples were collected from 140 hospitalized children. Age related reference data for the excretion of all three metabolites are reported. We suggest certain precautions that should be observed when using untimed samples and relating the results to creatinine excretion.

Adolescent

Comparison of the structure of the genes for outer membrane proteins P1 and P2 of Haemophilus influenzae type b.

Size and antigenic heterogeneity have been recognized in both outer membrane protein P1 and outer membrane protein P2 of Haemophilus influenzae type b. To determine the molecular basis for these differences, we have cloned and sequenced the structural genes for OMPs P1 and P2 from prototype isolates with the OMP subtypes 1H, 3L and 6U. The nucleotide and derived amino acid sequences of the P1 genes are characterized by three variable regions dispersed between highly conserved regions. The nucleic acid and derived amino acid sequences of the P2 genes are also highly conserved. The P2 genes from OMP subtype 1H and 3L isolates are identical. The sequence of the 6U gene differs by 13 nucleotides, resulting in 10 amino acid changes.

Bacterial Outer Membrane Proteins

Effects of recombinant methionyl bovine somatotropin (sometribove) in high producing cows milked three times daily.

Effects of daily sometribove administration on milk yield and composition, body condition score, BW, and SCC were evaluated in Holstein cows milked three times daily. Lactating cows (n =104) were assigned randomly to control or sometribove-treated (25 mg/d) groups. The experimental period was 16 wk, consisting of 2-wk pretreatment, 12-wk treatment, and 2-wk posttreatment periods. All cows were injected once daily starting at 53 to 180 d postpartum, housed in free stalls, and fed one of five total mixed rations according to milk production. Body weights were measured weekly, and body condition was scored biweekly. Milk yield was recorded daily, and weekly milk samples were analyzed for fat, protein, lactose, total solids, and SCC. Milk yield and milk protein were increased 18.8% (38.6 vs. 32.5 kg/d) and 3.3% (3.1 vs. 3.0%), respectively, whereas percentage of milk fat, lactose, SNF, SCC, and BW were unaffected by treatment. Overall average body condition scores were lower for the sometribove-treated group versus control (2.2 vs. 2.4). No apparent differences in the number of cows treated for mastitis, foot rot, displaced abomasum, or lameness were observed between treatment groups. Sometribove treatment significantly enhanced milk yield (6.1 kg/d) with no apparent negative effects on health in high producing cows milked three times per day.

Animals

The impact of the amended Ontario Mental Health Act (Bill 7) on patients discharging themselves from hospital against medical advice (AMA): a preliminary study.

Bill 7, the most recent amendment to the Ontario Mental Health Act was introduced in December 1986. It has resulted in some major changes to the practice of psychiatry, especially in provincial hospitals. We compared patients who had discharged themselves against medical advice (AMA) during the six months before the Bill was enacted, with those who discharged themselves AMA in the 12 months following. Significantly more patients discharged themselves AMA in the post- than the pre-Bill period. The majority of these were potentially treatable, acutely ill individuals with schizophrenia or affective disorder. We argue that Bill 7 has largely failed in its objective to improve the overall "quality of care" to psychiatric patients, at least in the short term.

Commitment of Persons with Psychiatric Disorders

Establishing a neonatal resuscitation team in community hospitals.

Recent national guidelines for neonatal resuscitation state that personnel trained in resuscitation skills should be immediately available for every delivery. Meeting this standard is a challenge for small community hospitals with limited staff and few 24-hour in-house physicians. We have developed a strategy for organizing neonatal resuscitation teams in community hospitals and describe our experience with establishing such teams in our region. Suggestions for implementation include: identifying a project organizer, involving all relevant staff in the decision making, writing a formal protocol, and planning a schedule for implementation. Often team members will be nurses or other professionals in expanded roles, the only stipulation being that they be immediately available and well trained. Recommendations are made for training and scheduling of neonatal resuscitation team members and for the contents of the resuscitation protocol. Barriers to successful implementation are discussed, including liability concerns or lack of confidence among team members, nonacceptance of expanded roles by other professionals, and difficulties with scheduling, equipment maintenance, and risk assignment. Nevertheless, successful establishment of a neonatal resuscitation team can effectively reduce the risk of neonatal asphyxia in small community hospitals.

Hospitals, Community

Origin of the autoreactive anti-type II collagen response. II. Specificities, antibody isotypes and usage of V gene families of anti-type II collagen B cells.

Autoantibodies play an important role in the pathogenesis of type II collagen-induced arthritis in mice. We have earlier reported a high frequency of cells producing anti-CII autoantibodies and a low frequency of cells producing multispecific antibodies, in regional lymph nodes 9 to 11 days after primary immunization with CII. It is shown here that anti-CII antibodies produced during primary immune response are IgG-antibodies mainly of IgG2a, IgG1 and IgG2b subclasses while IgM antibodies dominate primary responses elicited by OVA and denatured CII as analyzed with a large panel of hybridomas. Anti-CII antibodies generated during the primary response recognize at least five different epitopes on the CII molecule. The specificities of these antibodies for various epitopes result from combinational association of products encoded by genes derived from various VH and VK families and/or by the occurrence of somatic mutations. It is suggested that the primary anti-CII autoantibody response involves activation of memory B cells and is in this aspect different from the origin of "natural" autoantibodies.

Animals

Diversity of the outer membrane protein P2 gene from major clones of Haemophilus influenzae type b.

In previous studies, it has been demonstrated that outer membrane protein P2 from Haemophilus influenzae type b has porin activity and that antibody directed against P2 is protective in an infant rat bacteraemic model. Outer membrane protein subtyping has been employed to subclassify type b Haemophilus isolates. Strain MinnA has the outer membrane protein subtype 1H and is representative of the dominant clonal group of disease-producing isolates in the United States. In the present study, the P2 gene from strain MinnA was employed to probe EcoRI- and Pvull-digested chromosomal DNA from 24 Haemophilus influenzae type b isolates representative of the common outer membrane protein subtype groups observed throughout the world. Restriction fragment length polymorphisms were identified for the members of the outer membrane protein subtype 3L group, but not for the other subtypes examined. The P2 gene from each of four prototype isolates was then cloned, sequenced and compared to the previously reported sequence of the strain MinnA gene. The P2 gene from each of two isolates with the outer membrane protein subtype 3L was identical to the MinnA P2 sequence. The P2 gene from a subtype 2L isolate differed by a single nucleotide and the gene from a subtype 6U isolate differed by 13 nucleotides. Thus, the P2 protein is highly conserved among type b isolates.

Amino Acid Sequence

Comparative analysis of the structures of the outer membrane protein P1 genes from major clones of Haemophilus influenzae type b.

P1 outer membrane proteins from Haemophilus influenzae type b are heterogeneous antigenically and with respect to apparent molecular weight in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. For determination of the molecular basis for the differences in the P1 proteins, the genes for the P1 proteins from strain 1613, representative of outer membrane protein subtype 3L, and strain 8358, representative of outer membrane protein subtype 6U, were cloned, sequenced, and compared with the previously reported gene for the P1 protein from strain MinnA, a strain with the outer membrane protein subtype 1H. These prototype strains are representatives of the three major clonal families of H. influenzae type b responsible for invasive disease in diverse areas of the world. The nucleotide sequences of the P1 genes from strains 1613 and 8358 were 94 and 90% identical to the MinnA sequence, respectively. The derived amino acid sequences were 91 and 86% identical, respectively. Heterogeneity between the MinnA and 1613 proteins was largely localized to two short variable regions; the protein from strain 8538 contained a third variable region not observed in the other P1 proteins. Thus, the outer membrane protein P1 genes are highly conserved; the variable regions may code for the previously demonstrated strain-specific antigenic determinants.

Amino Acid Sequence

Idiopathic familial atrial cardiomyopathy with diffuse conduction block.

Isolated atrial cardiomyopathy is rare and familial idiopathic atrial cardiomyopathy has only been described once. We describe a case characterized by severely reduced atrial contractile function, intermittent atrial electrical standstill, diffuse interatrial, intraventricular and atrioventricular block, complicated by systemic embolism. Whilst this condition is undoubtedly rare, other cases may be being mistaken for simple sinoatrial disease.

Adult

Specificities and V genes encoding monoclonal autoantibodies from viable motheaten mice.

Several hundred hybridomas were obtained from 1-2-mo-old viable motheaten (mev) mice. Among the Ig-secreting hybridomas tested, greater than 50% (17/33) exhibited reactivity for autoantigens, supporting the idea that the Ly-1 B cells that predominate in mev mice contain frequent precursors of autoantibody-forming cells. Certain of the specificities of these autoantibodies correlated with the documented pathophysiology of mev mice (antithymocyte, -erythrocyte, -skin, -kidney, and -IgG); others were specific for autoantigens not previously observed in motheaten mice but though to be involved in other autoimmune diseases (e.g., intrinsic factor, transferrin, myelin basic protein, and thyroglobulin). About 2 of 3 (11/17) of the self-reactive antibodies exhibited multispecific binding activity for various autoantigens. Analysis by Northern blotting of the V gene families used in mev autoantibodies showed a random usage of VH families and a biased usage of four Vk gene families. Of 16 autoantibodies tested, 12 used a Vk gene from the Vk1, 4, 10, or 19 families. These patterns of Vk gene usage differ from nonautoimmune control animals. Overall, an immunoregulatory defect operating at a more generalized level than the VH or Vk loci, and due to a single gene mutation, appears to be responsible for the multiple immune abnormalities of mev mice.

Animals

Opioid withdrawal and naltrexone induction in 48-72 hours with minimal drop-out, using a modification of the naltrexone-clonidine technique.

Using clonidine, naltrexone, and diazepam, 60 withdrawals from heroin and other opioids involving 56 addicts were carried out with only one patient dropping out. In the last 23 cases, we used a modification of the standard technique, giving significantly higher doses of naltrexone and clonidine on the first day. This significantly reduced the average withdrawal time from 3.30 days to 2.32 days, despite lower clonidine dosage and significantly lower diazepam dosage on the second day. The speed, effectiveness, economy, and high acceptability of this withdrawal technique have implications for both private and state-funded treatment programmes.

Adolescent