Search PubMed⌕ Search

Biomedical subjects

K Murray

Publications and source records attributed to K Murray.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mutations of some critical amino acid residues in the hepatitis B virus surface antigen.

Amino acid substitutions at several positions in the surface antigen (HBsAg) of hepatitis B virus (HBV) in natural isolates and the products of recombinant DNA molecules have identified important residues for cross-reaction with specific antibodies (anti-HBs) and the induction of antibodies with certain serological specificities. In a further group of mutants described here, cysteine residues in a region believed to be significant of the a epitope have been changed to serines. Of the three adjacent cysteine residues at positions 137, 138 and 139, mutation of either of the flanking residues reduced cross-reactivity with polyclonal anti-HBs, while alteration of the central residue was relatively well-tolerated. Mutation of cysteine 149 to serine or of glycine 145 to arginine (imitating naturally occurring mutants), lysine, or glutamatic acid all led to loss of cross-reactivity with polyclonal antisera.

Amino Acid Sequence↗
PubMed1995

Immunoglobulin isotype modulation after administration of IL-12.

We have begun a series of experiments assessing the role of IL-12 in the humoral immune response. IL-12 is known to enhance cellular immunity causing a shift toward a Th1, as opposed to a Th2, response. IL-12 is also a potent stimulator of IFN-gamma production which, among other activities, modulates isotype expression particularly with respect to IgG2a. We have performed a series of experiments involving the concurrent dosing of mice with murine IL-12 and TNP-KLH followed by the monitoring of IgG1 and IgG2a anti-TNP responses and total IgG1 and IgG2a levels. Following administration of IL-12, specific anti-TNP titers showed an IgG2a increase while IgG1 responses were markedly lower than those exhibited by animals which did not receive IL-12. Total IgG1 levels in IL-12 treated mice remained at or near baseline while untreated mice demonstrated an increase in total IgG1 levels. In addition, lymph nodes from these mice were removed, stimulated with KLH and assayed for expression of murine IFN-gamma and IL-4. Murine IFN-gamma levels in supernatants obtained from IL-12 treated mice were elevated over those seen in untreated mice while IL-4 levels were suppressed.

Adjuvants, Immunologic↗
PubMed1995

Malignant change in enterocystoplasty: a histochemical assessment.

Increasing numbers of cases of malignant tumours occurring in enterocystoplasties are being reported. Material from five cases of adenocarcinoma arising in such patients were studied using standard mucin and carbohydrate lectin staining methods. Sections from the tumour and adjacent and distant mucosa were stained to determine the pattern of histochemical changes. The abnormal staining patterns seen suggest that the adenocarcinomata arising at the enterovesical anastomosis are of intestinal origin. A hypothesis is advanced to explain the pathogenesis of these tumours.

Adenocarcinoma↗
PubMed1995

Sequence evolution of the hypervariable region in the putative envelope region E2/NS1 of hepatitis C virus is correlated with specific humoral immune responses.

Sequence evolution of the hypervariable region 1 (HVR1) in the N terminus of E2/NS1 of hepatitis C virus (HCV) was studied retrospectively in six chimpanzees inoculated with the same genotype 1b strain, containing a unique predominant HVR1 sequence. Immediately after inoculation, all animals contained the same HVR predominant sequence. Two animals developed an acute self-limiting infection. Anti-HVR1 immunoglobulin G (IgG) was produced 40 to 60 days after inoculation and rapidly disappeared after normalization of transaminases. Another chimpanzee, previously infected with human immunodeficiency virus type 1, showed a delayed response to HVR1 epitopes after superinfection with HCV. No sequence variation of HVR1 was observed in these two animals during the transient viremia in the acute phase. Three other chimpanzees developed a chronic HCV infection. During follow up, sequence evolution occurred in two animals and their anti-HVR1 response remained at varying but detectable levels. The first mutations occurred immediately after the production of anti-HVR1 during the acute phase. However, IgM anti-HVR1 was not detectable. Remarkably, HVR1 sequences remained conserved for more than 6 years in another chronically infected animal. This correlated with the complete absence of detectable anti-HVR1 during this period. Seven years after inoculation, anti-HVR1 IgG was produced and coincided with an HVR1 alteration. These results strongly suggest the involvement of neutralizing anti-HVR antibodies in sequence evolution of HVR1 through immune selection.

Amino Acid Sequence↗
PubMed1995

Scottish neonatal intensive care units; a study of staff and parental attitudes.

The study takes a three stage approach to review Scottish unit policies, staff views and parents experiences of visiting and involvement with their low birthweight infant (1,750 gm or less) in a sample of Scottish neonatal intensive care units (NICUs). The study indicated that while most units had 'liberal' views regarding parental and family visiting some staff views were not in line with their unit policy and retained reservations about family visiting. Many parents reported visiting daily despite considerable 'social' and real costs. Unit differences emerged regarding the degree of parental involvement as measured by tasks carried out.

Adult↗
PubMed1995

Patterns of T lymphocyte clonal expansion in HLA-typed patients with juvenile rheumatoid arthritis.

OBJECTIVE: The presence of clonally expanded T lymphocytes appears to be a characteristic feature of autoimmune diseases, including juvenile rheumatoid arthritis (JRA), although the relevance of such clones to immunopathogenesis is not clear. Identification of clones specific for a disease and/or particular MHC haplotypes should help differentiate those of pathogenic importance. METHODS: A reverse transcriptase polymerase chain reaction assay for T cell receptor (TCR) complementarity determining region 3 (CDR3) length heterogeneity and cDNA sequencing were used to identify clonal expansion in synovial fluid (SF) samples obtained from 36 patients with JRA. RESULTS: The majority of patients had multiple synovial T cell clones using different TCR V beta families. Fifty-eight percent of these clonally expanded T cell populations used one of six TCR V beta families (V beta 2, V beta 8, V beta 14, V beta 16, V beta 17, and V beta 20). Patients with polyarticular, as opposed to pauciarticular, JRA had higher numbers of clones in joints. TCR V beta 8, V beta 14, V beta 16, and V beta 17 families were most frequently found in these clones. Overall, the most frequently used V beta family was V beta 20, which was observed in 18 of 36 SF samples. Of 18 patients exhibiting TCR V beta 20 clonal expansion, 14 (78%) had pauciarticular onset JRA. The V beta 20 association was especially strong in patients who possessed HLA-DR8+ haplotypes (p = 0.01, Fisher's exact test). SF from the patients who had other types of JRA (and other MHC haplotypes) did not show this association. CONCLUSION: The distinct clinical subtypes of JRA are characterized by different patterns of synovial T cell clonality. These findings imply that different molecular pathways underlie the development of arthritis in each subtype of JRA.

Amino Acid Sequence↗
PubMed1994

Longitudinal analysis of hepatitis C virus infection and genetic drift of the hypervariable region.

Hepatitis C virus (HCV) infections in a cohort of chimpanzees were studied retrospectively. All animals had been inoculated intravenously with materials derived from a single-source chimpanzee plasma implicated in non-A, non-B hepatitis, prepared by extensive ultracentrifugation. Anti-HCV and HCV RNA were monitored by the confirmatory line immunoassay and by an RNA-capture polymerase chain reaction method, respectively. In a chronically infected chimpanzee, HCV RNA was detectable after 32 days and throughout the acute phase, dropped transiently below detection level, and became detectable again. In 3 other chimpanzees with acute resolving infections, HCV RNA was detected 7-11 days after inoculation and became permanently undetectable after alanine aminotransferase normalization. Various anti-HCV profiles were detected among the chimpanzees. Analysis of the hypervariable region in E2/NS1 in 7 chimpanzees suggested genome stability on transmission, revealed different mutation frequencies during chronic infection, and suggested the importance of immune selection during chronic HCV infection.

Amino Acid Sequence↗
PubMed1994

Maternal reports of conscience development and temperament in young children.

Multiple manifestations of emerging conscience, their development, organization, and links with temperament were studied in 171 21-70-month-old children. A new parental report instrument was designed to measure conscience, with good psychometric qualities and predictive of children's behaviors in a laboratory. For most aspects of conscience, the major developmental shifts occurred around age 3.2 components of early conscience emerged in factor analyses: Affective Discomfort, significantly higher for girls, that encompassed guilt, apology, concern about good feelings with the parent following wrongdoing, and empathy with others, and Active Moral Regulation/Vigilance, which included confession and reparation following wrongdoing, internalization of rules of conduct (self-regulation), and concern about others' wrongdoing. Children's temperament, assessed by maternal reports, was associated with conscience. Low impulsivity and high inhibitory control were associated with Active Moral Regulation/Vigilance for both sexes and, for girls only, also with Affective Discomfort. For girls, temperamental reactivity related positively to Affective Discomfort and negatively to Active Moral Regulation/Vigilance.

Affect↗
PubMed1993

Hyperfractionated radiation therapy and bis-chlorethyl nitrosourea in the treatment of malignant glioma--possible advantage observed at 72.0 Gy in 1.2 Gy B.I.D. fractions: report of the Radiation Therapy Oncology Group Protocol 8302.

Between January 1983 and November 1987, the Radiation Therapy Oncology Group conducted a prospective, randomized, multi-institutional, dose searching Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma. Patients with anaplastic astrocytoma, or glioblastoma multiforme, age 18-70 years with a Karnofsky performance status of 40-100 were stratified according to age, Karnofsky performance status, and histology, and were randomized. Initially randomization was to one of three arms: 64.8 Gy, 72.0 Gy, and 76.8 Gy. Fractions of 1.2 Gy were given twice daily, 5 days per week, with intervals of 4 to 8 hr. All patients received bis-chlorethyl nitrosourea (BCNU) 80 mg/m2 on days 3, 4, 5 of radiation therapy and then every 8 weeks for 1 year. After acceptable rates of acute and late effects were found, the randomization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1. Out of 466 patients randomized, 435 were analyzed. The distribution of prognostic factors was comparable among the 76.8 Gy arm, 81.6 Gy arm, and the final randomization of the 72 Gy arm. The 64.8 Gy arm and the initial randomization of the 72 Gy arm had somewhat worse prognostic variables. Late radiation toxicity occurred in 1.3-6.8% of the patients, with a modest increase with increasing radiation dose. The best survival occurred in those patients treated with 72 Gy (median survival of 12.8 months overall, and 14 months for the final 72 Gy randomization). The Cox proportional hazards model confirmed the prognostic variables of age, histology and Karnofsky performance status. In addition, the longer interval of 4.5-8 hr was associated with a worse prognosis than the 4-4.4 hr interval (p = 0.0011). The difference in survival between the 81.6 Gy arm and the lower three arms approached significance (p = 0.078) with inferior survival observed in the 81.6 Gy arm. When therapy was evaluated by radiation therapy dose received (60-74.4 Gy compared with 74.5-84.0 Gy), the p value was 0.062 in favor of the lower dose range. Patients with anaplastic astrocytoma treated with 72 Gy by hyperfractionation + BCNU had at least as good a survival as those treated with 60 Gy by conventional fractionation + BCNU on Radiation Therapy Oncology Group protocols 7401 and 7918. This suggests that 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered by conventional fractionation.

Adult↗