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Biomedical subjects

K Murray

Publications and source records attributed to K Murray.

At least 127 records · Page 7Linked to original sources
PubMed1989

Mutants of the hepatitis B virus surface antigen that define some antigenically essential residues in the immunodominant a region.

The nature of the immunodominant a region of hepatitis B virus surface antigen (HBsAg) has been examined by mutation of specific amino acid residues. Proline 142 was required for the exhibition of full antigenicity. Replacement of cysteines 124 and 147 by serines drastically reduced or eliminated reactivity with antibodies to HBsAg, which implicates these two residues in stabilising the conformation of the antigen. The a region of HBsAg has also been shown to influence both the immunoreactivity of the adjacent subtype antigenic region, despite being immunologically distinct from it, and the ability of the antigen to interact with a subtype-specific monoclonal antibody. These results emphasise the importance of the polypeptide region between cysteine residues 124 and 147 in determining a antigenicity, as well as manifestation of the subtype of HBsAg, and reinforce the view that these are conformational epitopes.

Amino Acid Sequence↗
PubMed1989

Mutations that change the immunological subtype of hepatitis B virus surface antigen and distinguish between antigenic and immunogenic determination.

The molecular basis of the d or y immunological subtype of hepatitis B virus (HBV) surface antigen (HBsAg) has been investigated by mutation of specific amino acid residues. When combined with substitution of serine 113 by threonine, replacement of arginine 122 by lysine or of tyrosine 134 by phenylalanine, or both of these changes, altered the antigenic subtype of HBsAg from y+d- to y+d+. These same mutations had a more dramatic effect on the subtype of antibodies induced by the antigens, a combination of all three mutations completely changing the subtype from y to d. Our study thus identifies residues in HBsAg that not only affect the subtype but discriminate between changes in antigenic and immunogenic behaviour. It also shows how the y and d subtypes may be manifest by the same molecule.

Amino Acid Sequence↗
PubMed1989

Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics.

Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood pressure (MAP) were also determined. Nifedipine increased ICG clearance by 14% and decreased t1/2 by 26%. Propranolol decreased ICG clearance by 21% and increased t1/2 42%. Nifedipine and propranolol given together increased ICG clearance 63% and decreased t1/2 by 19%. All changes were statistically significant. Propranolol given after multiple doses of nifedipine did not change ICG kinetic parameters. Propranolol Cmax, tmax, oral clearance, and t1/2 did not change after nifedipine therapy. However, partial propranolol AUC values between 0-0.33, 0-0.5, 0-1.0 and 0-1.5 h were significantly larger after single and multiple doses of nifedipine indicating higher propranolol concentrations during the absorption phase. Heart rate and MAP did not change after nifedipine treatment. Similar declines in heart rate and MAP occurred after propranolol alone and propranolol after single and multiple doses of nifedipine.

Administration, Oral↗
PubMed1989

Immunogenicity of peptide fusions to hepatitis B virus core antigen.

Several gene fusions have been constructed in which coding sequences for antigenic regions of the pre-S sequences of hepatitis B virus, hepatitis B surface antigen, and the envelope protein of human immunodeficiency virus were linked to the 3' end of that for the first 144 residues of hepatitis B core antigen. The sequences were expressed efficiently in Escherichia coli to give stable products that assembled to form particles morphologically similar to hepatitis B core antigen itself. The products exhibited the antigenic and immunogenic characteristics of both the hepatitis B core antigen epitopes and the epitopes carried by the additional sequences, thus illustrating the value of such proteins as immunological reagents and potential vaccines.

Amino Acid Sequence↗
PubMed1989

Bone marrow transplantation for children with severe aplastic anemia: use of donors other than HLA-identical siblings.

Eighty-five percent of untransfused and 70% of transfused patients with severe aplastic anemia (SAA) are cured with bone marrow transplants from histocompatible sibling donors. Use of partially matched family donors or unrelated donors has been relatively unsuccessful because of high incidences of graft rejection and graft-versus-host disease (GVHD). Thirteen children with SAA received marrow grafts from alternative donors (sibling 4, parent 5, unrelated 4). The first three patients were pretreated with cyclophosphamide (CYCLO) +/- irradiation and received methotrexate for GVHD prophylaxis. Subsequent children were pretreated with CYCLO + high-dose cytosine arabinoside + methylprednisolone + total body irradiation, had monoclonal antibody T-cell depletion of the donor marrow, and received cyclosporine for GVHD prophylaxis. Three heavily transfused patients with haploidentical-related donors failed to engraft and died. All 10 patients with more closely matched donors engrafted. Acute GVHD was grade II in only one patient (non-T-depleted); this patient is the only one with severe chronic GVHD. Three engrafted patients died (Pneumocystis pneumonia, systemic parainfluenza, venocclusive disease). Seven children are alive 33+ to 2,692+ days. Donors for the survivors were siblings 3, parent 1, unrelated 3. These data suggest that bone marrow transplantation from closely matched donors other than histocompatible siblings can be effective therapy for SAA if an intensive conditioning regimen is used. These results must be confirmed with larger numbers and longer follow-up.

Adolescent↗
PubMed1988

Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell.

The mitogens which modulate cell-cell interactions during development of the central nervous system are unknown. One of the few interactions sufficiently well understood to allow identification of such molecules involves the two glial lineages which make up the rat optic nerve. One population of glial cells in this tissue, the type-1 astrocytes, secrete a soluble factor(s) which promotes division of a second population of bipotential oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells; these progenitors give rise to oligodendrocytes, which myelinate large axons in the CNS, and type-2 astrocytes, which enwrap bare axons at nodes of Ranvier. Type-1 astrocytes also promote progenitor motility, and inhibit the premature differentiation of progenitors into oligodendrocytes which occur when these cells are grown in the absence of type-1 astrocytes. We have now found that platelet-derived growth factor mimics the effects of type-1 astrocytes on O-2A progenitor cells, and antibodies to PDGF block the effects of type-1 astrocytes.

Animals↗
PubMed1988

Application of recombinant DNA techniques in the development of viral vaccines.

The wide repertoire of methods developed for the construction and manipulation of recombinant DNA molecules enable viral genomes to be cloned and their genes expressed, in whole or in part, in microbial or animal cells in culture. This provides a ready source of many viral components that are otherwise difficult to obtain and in some cases were previously unknown. Although immediate applications for vaccine development have concentrated principally upon envelope proteins, the immunological importance of other viral components is being increasingly recognized. Hepatitis B virus is used here to exemplify the application of recombinant DNA technology to the development of subunit vaccines and to illustrate their value in studies of other viral proteins with particular emphasis on the role of the core antigen in providing protection against viral infection and hence its potential in vaccine development.

Amino Acid Sequence↗
PubMed1988

Selective application of cervical spine radiography in alert victims of blunt trauma: a prospective study.

Four hundred sixty-seven adult victims of blunt trauma undergoing cervical spine radiography (CSR) were prospectively studied to identify any clinical parameters which would aid in the selective application of CSR. Eight persons (1.7%), six of whom were alert and two who presented comatose, sustained cervical spine injuries. In this study, persons injured in falls demonstrated a statistically significant greater risk of cervical spine injury compared to those injured in motor vehicle accidents (p = 0.001). In alert trauma victims, a statistical correlation with cervical spine injury was noted for individuals who had complaints of neck discomfort (p = 0.028) and for patients who manifested tenderness to neck palpation (p = 0.000039). No cervical spine injury was noted in any alert, not intoxicated, neurologically intact patient who had no complaints of neck discomfort upon questioning or palpation. We conclude that alert trauma victims with no complaints of neck discomfort upon questioning and with no tenderness on neck palpation need not undergo CSR.

Adolescent↗
PubMed1988

Epiphyseal growth plate: evaluation with modified coronal CT.

A method of modified coronal computed tomography (CT) was developed for examination of epiphyseal growth plate arrest and neoplasms near the growth plate. Twenty-four patients were examined with this technique (26 examinations). In all cases, the growth plate and adjacent regions were well demonstrated.

Adolescent↗
PubMed1987

The Leeuwenhoek lecture, 1985. A molecular biologist's view of viral hepatitis.

Three forms of viral hepatitis can be distinguished serologically. Hepatitis A virus is a picornavirus, which is being studied increasingly after its propagation in cell cultures. The B virus (HBV) is the prototype of a family now termed hepadna viruses and is by far the best understood. The third, by exclusion, is non-A non-B, about which little else is known. Molecular cloning methods enable copies of viral genes to be propagated and analysed quite readily and provide the means for isolation and expression of individual genes in microbial and animal cells. Determination of the nucleotide sequences of HBV DNA revealed its genetic organization and so guided studies of the mechanism of gene expression both in infected animals and cultures of transformed cells. Replication of the viral genome has also been studied in natural infections, particularly with duck HBV, but also with the human virus. Expression of HBV genes in microbial cells is valuable as a source of antigens for diagnostic reagents and vaccine preparations, but has also been of consequence for the identification of viral gene products not previously recognized and which are of considerable current interest. The methods and materials now available provide additional opportunities for inquiring into the course of viral infection, replication of the virus and, for HBV, the possible role in the development of hepatomas of integration of the viral genome into the host chromosome.

Genes, Viral↗
PubMed1987

Protective immunisation against hepatitis B with an internal antigen of the virus.

Preparations of hepatitis B virus (HBV) core antigen (HBcAg) synthesised in Escherichia coli have been shown previously to confer partial immunity against infection by the virus [Murray, Bruce, Hinnen, Wingfield, van Eerd, de Reus, and Schellekens: EMBO Journal 3:645-650, 1984]. In a further experiment reported here, immunisation of chimpanzees with a similar preparation of HBcAg that had been treated with sodium dodecyl sulphate in order to expose e antigen epitopes was found to protect one animal completely and another quite substantially upon challenge with the virus. The results are used to support the argument for trials in humans of a vaccine against HBV based upon or containing HBcAg and its e antigen derivative, and in discussion of a more general role for internal antigens in generating immunity against viral infection.

Animals↗
PubMed1987

An epidemiological study of high school ice hockey injuries.

Between 1976 and 1983, 42 spinal cord injuries among ice hockey participants were documented in Canada; within a recent 3-week period, three cases involving fractured necks were reported in a metropolitan area of Minnesota. The purpose of this comprehensive epidemiological study was to document rates, types, and severities of injuries incurred among high school varsity hockey players in Minnesota, as a result of participation in the 1982-1983 season, and to determine the variables associated with these injuries. Within a 30-mile radius of the state's major metropolitan area, 12 high school varsity hockey teams were selected for participation. Specific techniques were used to ensure confidentiality, high response rates, and validation of information. Among the players an injury rate of 75 injuries per 100 players was documented. Head and neck injuries accounted for 22% of the total injuries. Increased risks of injury were associated with multiple health-care provision variables and equipment utilized. Potential strategies are identified as a result of these findings.

Adolescent↗
PubMed1987

The "congenital" wide bladder neck anomaly: a common cause of incontinence in children.

In a study of 251 children (108 boys, 143 girls) undergoing videourodynamic studies for the assessment of non-neuropathic bladder dysfunction, 45 (19%) were found to have a wide bladder neck as their primary abnormality. Based on these studies there is evidence that the wide bladder neck anomaly is congenital in origin. In addition to producing significant urinary symptoms in childhood, this anomaly may provide a basis for stress incontinence in later life.

Adolescent↗
PubMed1987

Secreto-motor function of intestinal segments used in lower urinary tract reconstruction.

Mucus excretion, sialic acid excretion and secretory IgA (sIgA) production from patients with a substitution caecocystoplasty (20), augmentation "clam" ileocystoplasty (20) or ileal conduit (10) were measured. Significant amounts of all of these substances were present in the urine of reconstructed patients and showed no evidence of diminution with time. Motility was studied by videocystourethrography. In patients with a neuropathic aetiology the amplitude of contractions was significantly increased and produced incontinence. The results demonstrate that intestinal secreto-motor function in gut segments incorporated into the lower urinary tract continues normally and must be taken into account when considering the long-term management of these patients.

Colon↗