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Biomedical subjects

D Harris

Publications and source records attributed to D Harris.

At least 163 records · Page 9Linked to original sources
PubMed1994

Persistence of self-renewing leukemia cell progenitors during remission in children with B-precursor acute lymphoblastic leukemia.

No effective therapy is available for the majority of the 30-40% of children with acute lymphoblastic leukemia (ALL) who relapse. Since the morphologically undetectable, or occult, leukemia cells that persist during remission originate from the clone present at diagnosis, may also have both the capability to sustain the disease and to give rise to relapse, we are evaluating a method of identifying them. We have combined, for the first time, an ALL blast colony assay (BCA) and the polymerase chain reaction (PCR) to isolate residual leukemia cells in remission bone marrow aspirate specimens from eight patients with B-precursor ALL during early continuation therapy. We found colony-forming leukemia cells with in vitro self-renewal capability that survived chemotherapy for 15 months after diagnosis in all sequential specimens from these patients. To verify the leukemic nature of these cells their DNA was amplified by PCR and the product directly sequenced. In every case, the VHDJH sequence observed at diagnosis was found. None of the patients relapsed during this early phase of their treatment, consistent with the observation that patients with B-precursor ALL experience recurrence late in their course. Since it is possible that some of these persistent leukemia cells belong to the leukemia progenitor cell population that sustains the disease, the study of them could provide the means to determine the mechanisms of relapse.

Adolescent↗
PubMed1993

Lymphotoxin is an autocrine growth factor for Epstein-Barr virus-infected B cell lines.

Because human lymphotoxin (LT) was originally isolated from a lymphoblastoid cell line, we investigated the role of this molecule in three newly established Epstein-Barr virus (EBV)-infected human B cell lines. These lines were derived from acute lymphoblastic leukemia (Z-6), myelodysplastic syndrome (Z-43), and acute myelogenous leukemia (Z-55) patients who had a prior EBV infection. Each lymphoblastoid cell line had a karyotype that was different from that of the original parent leukemic cells, and all expressed B cell, but not T cell or myeloid surface markers. In all three lines, rearranged immunoglobulin heavy chain joining region (JH) bands were found, and the presence of EBV DNA was confirmed by Southern blotting. Z-6, Z-43, and Z-55 cell lines constitutively produced 192, 48, and 78 U/ml LT, respectively, as assessed by a cytotoxicity assay and antibody neutralization. Levels of tumor necrosis factor (TNF) were undetectable. Scatchard analysis revealed that all the cell lines expressed high-affinity TNF/LT receptors with receptor densities of 4197, 1258, and 1209 sites/cell on Z-6, Z-43, and Z-55, respectively. Furthermore, labeled TNF binding could be reversed by both unlabeled TNF, as well as by LT. Studies with p60 and p80 receptor-specific antibodies revealed that the three lines expressed primarily the p80 form of the TNF receptor. When studied in a clonogenic assay, exogenous LT stimulated proliferation of all three cell lines in a dose-dependent fashion at concentrations ranging from 25 to 500 U/ml. Similar results were obtained with [3H]TdR incorporation. Monoclonal anti-LT neutralizing antibodies at concentrations of 25-500 U/ml inhibited cellular multiplication in a dose-dependent manner. It is interesting that in spite of a common receptor, TNF (1,000 U/ml) had no direct effect on Z-55 cell growth, whereas it partially reversed the stimulatory effect of exogenous LT. In addition, TNF inhibited Z-6 and Z-43 cell proliferation, and its suppressive effect was reversed by exogenous LT. Both p80 and p60 forms of soluble TNF receptors suppressed the lymphoblastoid cell line proliferation and their inhibitory effect was partially reversed by LT. Our data suggest that (a) LT is an autocrine growth factor for EBV-transformed lymphoblastoid B cell lines; and (b) anti-LT antibodies, soluble TNF/LT receptors, and TNF itself can suppress the growth of lymphoblastoid cells, probably by modulating or competing with LT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Identification, classification, and analysis of beta-bulges in proteins.

A beta-bulge is a region of irregularity in a beta-sheet involving two beta-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in beta-sheets were identified and classified automatically, extending the definition of beta-bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson, D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of beta-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges. Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, beta-bulges produce two main changes in the structure of a beta-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands.

Amino Acid Sequence↗
PubMed1993

A psychophysiological approach to the assessment of work underload.

The findings of a laboratory investigation of the relationship between the subjective and physiological components of work underload are reported. The subjective component is described in terms of the subjective work underload checklist, mental effort, and cognitive arousal. The physiological component is defined in terms of heart rate and heart rate variability. Evidence for an increase in work underload with a decrease in heart rate is provided. The relevance of this research to the aerospace environment is discussed and the need to investigate the behavioural component of work underload emphasized.

Adult↗
PubMed1993

Levobunolol compared to dipivefrin in African American patients with open angle glaucoma.

The prevalence of open angle glaucoma is disproportionately high in the African American population. Information about the effectiveness of anti-glaucoma medications in an exclusively African American population is lacking. We treated both eyes of 38 African American patients who have stable open angle glaucoma with either levobunolol b.i.d. or dipivefrin b.i.d. to evaluate the effectiveness of each drug in lowering intraocular pressure. Patients were treated for six weeks following a two week washout period. We measured intraocular pressure levels after one, three, and six weeks. Each medication produced a statistically significant decrease in intraocular pressure by week one. The mean pre-treatment pressure of 24.4 mmHg in the levobunolol was reduced to 17.0 mmHg by week six. The mean pre-treatment pressure of 25.4 mmHg in the dipivefrin treated group was reduced to 18.2 mmHg by week six. There was not a statistically significant difference in the pre-treatment or the final pressure between the two groups. Both levobunolol and dipivefrin produce a statistically significant decrease in intraocular pressure in African American patients with open angle glaucoma.

Adult↗
PubMed1993

The use of a computer-assisted telephone interview technique in a general practice research study.

We describe the principles and practice of computer-assisted telephone interviewing, and its successful deployment in a general practice-based research study into the referral behaviour of general practitioners (GPs) in the Grampian region of Scotland. Participating GPs were interviewed concerning the acceptability of the method. It proved to be an efficient and acceptable method for collecting data from a large number of practitioners in this large geographical area. Our experience confirms that this efficient method of data collection could be much more widely utilized in primary care research.

Computers↗
PubMed1993

Expression of the Mycobacterium tuberculosis 19-kilodalton antigen in Mycobacterium smegmatis: immunological analysis and evidence of glycosylation.

The gene encoding a 19-kDa antigen from Mycobacterium tuberculosis was expressed as a recombinant protein in the rapid-growing species Mycobacterium smegmatis. The recombinant antigen was expressed at a level approximately ninefold higher than in M. tuberculosis and, like the native antigen, was found in the pellet fraction after high-speed centrifugation of bacterial extracts. The 19-kDa antigen in crude bacterial extracts, and the purified recombinant antigen, bound strongly to concanavalin A, indicating the possibility of posttranslational glycosylation. The recombinant antigen stimulated T-cell proliferation in vitro when added to assays either in the form of whole recombinant bacteria or as a purified protein. Homologous expression of mycobacterial antigens in a rapid-growing mycobacterial host may be particularly useful for the immunological characterization of proteins which are subject to posttranslational modification.

Amino Acid Sequence↗
PubMed1993

The prevalence of thought disorder in personality-disordered outpatients.

Patients with borderline personality disorder (BPD) have been found to exhibit thought-disordered responses on unstructured psychological tests, but not on more structured tests. My study compared outpatients diagnosed with BPD to those who qualified for other personality disorders (OPD). Johnston and Holzman's (1979) Thought Disorder Index was applied to the Rorschach and Wechsler Adult Intelligence Scale-Revised (WAIS-R) protocols of two outpatient groups. The results of this study demonstrated that the BPD group produced a significantly greater number of thought-disordered responses on the Rorschach but not on the WAIS-R compared to the OPD group. Thus, the test pattern of individuals with BPD was confirmed by this study and successfully differentiated these patients from OPD outpatients. Further exploration of the degree of thought disorder on structured versus unstructured tests is suggested.

Adult↗
PubMed1993

The effect of preference for rock music on magnitude-estimation scaling behavior in young adults.

The purpose of the present study was to examine the effect of preference for rock music on magnitude-estimation scaling behavior in young adults. Two groups of young adults, 20 who liked rock music and 20 who did not like rock music, were tested. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of a 10-second sample of rock music. Analysis indicated that there was a difference in performance by the two groups of subjects on the magnitude-estimation scaling task. The subjects who liked rock music provided significantly lower mean numerical responses than the subjects who did not like rock music for all nine suprathreshold intensities.

Adolescent↗
PubMed1993

Effect of preference for rock music on magnitude-production scaling behavior in young adults: a validation.

The purpose of the presence study was to examine the effect of preference for rock music on magnitude-production scaling behavior in young adults as an attempt to validate further the 1993 magnitude-estimation scaling results obtained by Fucci, Harris, Petrosino, and Banks. Two groups of young adults, 20 who liked rock music and 20 who disliked rock music, were tested. Subjects were instructed to adjust the intensity of a 10-sec. sample of rock music in response to seven written stimuli presented in random order. Analysis indicated that there was a significant difference in performance by the two groups of subjects on the magnitude-production scaling task. Those subjects who liked rock music adjusted the intensity of the music to higher levels than did the subjects who disliked rock music.

Adolescent↗
PubMed1992

Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors.

Interleukin-1 (IL-1) has recently been reported to play an important role in acute myelogenous leukemia (AML) blast proliferation. We therefore investigated the effect of soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) on the growth of AML bone marrow blast progenitors from 25 patients. In the AML blast colony culture assay, sIL-1R and IL-1RA inhibited blast colony-forming cell replication in a dose-dependent fashion, at concentrations ranging from 10 to 500 ng/mL (sIL-1R) and 10 to 1,000 ng/mL (IL-1RA), and their inhibitory effect was partially reversed by IL-1 beta. A similar inhibitory effect was also noted with the use of anti-IL-1 beta neutralizing antibodies. When AML blast progenitors were grown either in the presence of fetal calf serum (FCS) alone or with one of the following: phytohemagglutinin leukocyte-conditioned medium (PHA-LCM), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, interleukin-3 (IL-3), or stem cell factor (SCF), addition of 100 ng/mL sIL-1R or IL-1RA inhibited blast colony formation by 3% to 96% and 2% to 97%, respectively. In sharp contrast, neither of these IL-1-inhibitory molecules significantly inhibited proliferation of normal marrow hematopoietic progenitors. Lysates of 2 x 10(7) low-density AML marrow cells were tested for intrinsic IL-1 beta content using an enzyme-linked immunoadsorbant assay (ELISA). Samples from five of six patients showed high concentrations (ranging from 501 to 2,041 pg), whereas 2 x 10(7) cells from two normal marrow aspirates yielded 54.6 pg of IL-1 beta. AML blast colony-forming cells from all six patients were inhibited by sIL-1R, IL-1RA, or both. Incubation of nine samples of AML low-density cells with either sIL-1R or IL-1RA reduced GM-CSF concentrations in cell lysates, and supernatants from nine (P less than .01) and six samples (P less than .037), respectively, and G-CSF concentration in lysates from six of nine samples (P less than .03), and in supernatants from five of six samples (P less than .06) when studied by ELISAs. Our data implicate IL-1 in AML blast proliferation and suggest the potential benefits of using IL-1-inhibitory molecules in future therapies for AML.

Adult↗