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Biomedical subjects

J Dunn

Publications and source records attributed to J Dunn.

At least 145 records · Page 8Linked to original sources
PubMed1992

Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis. The Medical Research Council Working Party for Leukaemia in Adults.

Both melphalan and cyclophosphamide increase life expectancy in patients with myelomatosis, but few large randomised studies have compared combination chemotherapy regimens with these single agents. In the Vth MRC myelomatosis trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU, cyclophosphamide, and melphalan) as first-line treatment was significantly longer than that of 316 patients given intermittent melphalan (M7) (p = 0.0003). The 75%, median, and 25% survivals were 7, 24, and 42 months, respectively, with M7 and 10, 32, and 56 months, respectively, with ABCM. Stable disease with few symptoms (plateau) was achieved by 61% of patients given ABCM and 49% of those given M7 (p = 0.004). Myelotoxicity was comparable between regimens. Cross-trial analysis suggests that M7 is comparable to melphalan and prednisone or melphalan, prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth MRC trials is comparable; and that ABCM gave better survival than intermittent melphalan regimens in the prognostic groups analysed. The results indicate that ABCM is an acceptable regimen that is more effective than melphalan, with or without prednisone, for first-line treatment of myelomatosis.

Aged↗
PubMed1992

Talk with your mother or your sibling? Developmental changes in early family conversations about feelings.

Developmental changes in the pattern of family conversations and talk about feelings were examined in a longitudinal study of 50 families observed at home when the second-born children were 33 and 47 months old. Significant increases were noted in the total amount of talk and the frequency of talk about feelings between sibling pairs as well as decreases in the amount of mother-child conversation and references to feelings. Differences in whose feelings were discussed and in the context of references to feelings were found for mother-child and sibling-child dyads. Developmental changes in the children's use of feeling state language co-occurred with the increase in interaction between children and their siblings. The findings contrast the "complementary" nature of mother-child interaction and the "reciprocal" nature of child-sibling interaction and support the argument that the quality of particular relationships influences the use children make of their communicative competence.

Child Development↗
PubMed1992

Adversities in childhood: siblings' experiences, and their relations to self-esteem.

The prevalence and negative impact of life events and adversities over a 3-year period on 80 children participating in a longitudinal study of siblings was examined. The scenarios of 256 events were rated by a child psychiatrist for negative impact on both siblings (aged 6 and 8-10 years, respectively). Only one of the 80 children had not experienced at least one major event. The majority (69%) of life events with negative impact and adversities were not shared by siblings. The relations between the impact of these adversities and children's perceived self-competence, temperament, and their mothers' mood were examined. The number of life events with negative impact was negatively correlated with children's perceived self-competence, an association apparently not mediated by children's temperament nor by maternal mood.

Child↗
PubMed1992

Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor.

The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice.

3T3 Cells↗
PubMed1991

Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein.

Granulocyte/macrophage colony-stimulating factor-interleukin 3 (GM-CSF-IL-3) fusion proteins were generated by construction of a plasmid in which the coding regions of human GM-CSF and IL-3 cDNAs were connected by a synthetic linker sequence followed by subsequent expression in yeast. Both GM-CSF-IL-3 and IL-3-GM-CSF fusion proteins were purified to homogeneity and shown to bind to cell-surface receptors through either their GM-CSF or IL-3 domains. The fusion proteins exhibited enhanced receptor affinity, proliferative activity, and hematopoietic colony-stimulating activity compared with either IL-3 and/or GM-CSF alone. This suggests that GM-CSF-IL-3 fusion proteins may hold future promise as therapeutic agents.

Base Sequence↗
PubMed1991

Bacteriophage T7 morphogenesis and gene 10 frameshifting in Escherichia coli showing different degrees of ribosomal fidelity.

Bacteriophage T7 infection has been studied in Escherichia coli strains showing both increased and decreased ribosome fidelity and in the presence of streptomycin, which stimulates translational misreading, in an effort to determine effects on the apparent programmed translational frameshift that occurs during synthesis of the gene 10 capsid protein. Quantitation of the protein bands from SDS-PAGE failed to detect any significant effects on the amounts of the shifted 10B protein relative to the in-frame 10A protein under all fidelity conditions tested. However, any changes in fidelity conditions led to inhibition of phage morphogenesis in single-step growth experiments, which could not be accounted for by reduced amounts of phage protein synthesis, nor, at least in the case of decreased accuracy, by reduced amounts of phage DNA synthesis. Reduction in phage DNA synthesis did appear to account for a substantial proportion of the reduction in phage yield seen under conditions of increased accuracy. Similar effects of varying ribosomal fidelity on growth were also seen with phage T3, and to a lesser extent with phage T4. The absence of change in the high-frequency T7 gene 10 frameshift differs from earlier reports that ribosomal fidelity affects low-frequency frameshift errors.

Capsid↗
PubMed1991

Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.

Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.

Aged↗
PubMed1991

Why are siblings so different? The significance of differences in sibling experiences within the family.

Siblings, who are 50% similar genetically and grow up within the same family, nevertheless differ markedly in personality and psychopathology, and most of these sibling differences cannot be explained by genetic factors. These findings from the field of behavioral genetics imply that within-family processes that lead to sibling differences, called nonshared environment, are crucial for understanding environmental influences on individual development. Such nonshared environmental influences cannot be identified by the conventional strategy of comparing one child per family on a family-by-family basis; what is needed are studies of siblings that focus on why they are so different. The implications of these findings for investigating family process are outlined, and research is reviewed that explores the extent to which siblings in a family have different experiences, and that begins to assess links between such differential experiences and developmental outcomes.

Family↗
PubMed1991

Power of oesophageal peristalsis can be controlled voluntarily.

The hypothesis that oesophageal peristalsis can be modified voluntarily was explored. Six healthy male volunteers and eight female patients with angina like chest pain underwent oesophageal manometry. Each was asked to take a series of swallows, and to vary their size, in random order, by taking either a big gulp or a little swallow. None of the subjects experienced difficulty in doing so. In both groups the amplitude of oesophageal contractions were significantly greater after big gulps than little swallows (p less than 0.01) and this was true for wet (82.0 v 68.9 mmHg) and dry swallows (52.3 v 43.3 mmHg). For the patients' wet swallows the mean values were 73.0 and 56.0 mmHg. Thus, the amplitude of oesophageal peristalsis can be controlled voluntarily. This effect may account for some of the within subject variation in the amplitude of oesophageal contractions. During oesophageal manometry subjects should be encouraged to standardise the size of their swallows whenever possible. Patients with symptoms related to abnormal oesophageal peristalsis such as dysphagia, heartburn, and chest pain may benefit from biofeedback training.

Adult↗
PubMed1991

Young children's understanding of other people's feelings and beliefs: individual differences and their antecedents.

Individual differences in young children's understanding of others' feelings and in their ability to explain human action in terms of beliefs, and the earlier correlates of these differences, were studied with 50 children observed at home with mother and sibling at 33 months, then tested at 40 months on affective-labeling, perspective-taking, and false-belief tasks. Individual differences in social understanding were marked; a third of the children offered explanations of actions in terms of false belief, though few predicted actions on the basis of beliefs. These differences were associated with participation in family discourse about feelings and causality 7 months earlier, verbal fluency of mother and child, and cooperative interaction with the sibling. Differences in understanding feelings were also associated with the discourse measures, the quality of mother-sibling interaction, SES, and gender, with girls more successful than boys. The results support the view that discourse about the social world may in part mediate the key conceptual advances reflected in the social cognition tasks; interaction between child and sibling and the relationships between other family members are also implicated in the growth of social understanding.

Affect↗
PubMed1991

Analysis of bacteriophage T7 gene 10A and frameshifted 10B proteins.

Bacteriophage T7 capsid protein 10B has previously been proposed to arise by a translational frameshift near the 3' end of the capsid gene 10A coding sequence, adding an additional 53 amino acid residues to the carboxyl-terminal end of the protein. Here we show by peptide mapping experiments as well as by direct partial sequence analysis of an overlapping "junction" peptide, that 10B is in fact related to 10A by a -1 switch in reading frame in a narrow region near the carboxy terminus of 10A. Peptide mapping experiments demonstrate that 10A and 10B have the same amino terminus as well as virtually identical methionine-labeled peptide maps. However, the predicted unique carboxyl-terminal peptide from 10B was also identified. An overlapping peptide was isolated from 10B which spans the junction region in which the proposed translational frameshift is thought to occur. Partial sequencing of this junction peptide confirms a -1 frameshift within the last few codons of 10A.

Amino Acid Sequence↗
PubMed1991

Demonstration of direct involvement of cytokines in graft-versus-host reactions using an in vitro human skin explant model.

A human skin explant model was used to investigate the role of cytokines in graft-versus-host reactions (GVHR). Responder cells from HLA mismatched mixed lymphocyte cultures (MLC) produced GVHR (Grades I-III) in skin explant assays. Cell-free supernatants from these experiments also induced similar histopathological changes in the skin. The greatest degree of correlation between the GVHR observed with responder cells and the supernatant was shown with CD4 enriched MLC (p less than 0.001). Supernatants were assayed for tumour necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN gamma) and CD4 enriched MLC populations produced high levels of these cytokines. These results correlated with the grade of GVHR observed in skin explant assays. The GVHR produced by the supernatant alone could be inhibited by both anti-IFN gamma and anti-TNF alpha polyclonal antibodies. The results suggest that TNF alpha and IFN gamma are directly involved in tissue damage during graft-versus-host disease in allogeneic transplant in man.

Cytokines↗