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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin-1 alpha mediates an alternative pathway for the antiproliferative action of poly(I.C) on human endothelial cells.

The antiproliferative effect of double-stranded RNA (dsRNA) on human tumor and normal cells has been well established. However, the genes involved in the dsRNA-induced antiproliferative response and the molecular mechanisms by which this occurs remain less well defined. We have studied the ability of synthetic dsRNA, polyinosinic:polycytidylic acid (poly(I.C)) to modify human umbilical vein endothelial cell (HUVEC) growth and report that poly(I.C) induces a dose-dependent inhibition of HUVEC proliferation in vitro. In addition, the mRNA levels for the cytokines interleukin-1 alpha (IL-1 alpha) and interferon-beta 1 are induced in poly(I.C)-treated cells. Moreover, the growth inhibitory effects of poly(I.C) are relieved when cells are grown in the presence of an IL-1 alpha antisense oligonucleotide to the human IL-1 alpha transcript. Thus, the effects of poly(I.C) appear to be mediated, in part, through the function of IL-1 alpha, suggesting an alternative pathway for dsRNA-mediated inhibition of human endothelial cell growth.

Base Sequence↗
PubMed1992

RNA sequence analysis shows that the symbionts in the ciliate Metopus contortus are polymorphs of a single methanogen species.

The polymerase chain reaction was used to amplify and partially sequence the 16S ribosomal RNA genes of symbiotic bacteria within the anaerobic ciliate Metopus contortus. In situ probing with fluorescent oligonucleotides showed that the amplified sequences originated from a single species of archaebacterium which is closely related to Methanocorpusculum parvum. The probed symbionts exhibited a variety of shapes and sizes. These data support the hypothesis, first proposed on the basis of electron microscopy, that the symbionts undergo a morphological transformation as part of the symbiotic process.

Animals↗
PubMed1992

Engineered iron oxide-adhesion mutants of the Escherichia coli phage lambda receptor.

Escherichia coli able to specifically adhere to iron oxide and not adhere to other metal oxides were constructed by genetic engineering. Concatamers of random oligonucleotides were introduced into a portion of a plasmid-borne lamB gene encoding an external domain of the phage lambda receptor. Bacteria able to adhere to iron oxide were selected by serial enrichment from the population of plasmid transformants. The concatameric nature of the inserted DNA allows a genetic analysis analogous to exons shuffling. Results of this genetic analysis indicate that in some isolates, part of the binding site is encoded by flanking vector sequences. This strategy may prove generally useful for identifying protein sequences able to recognize specific surfaces.

Amino Acid Sequence↗
PubMed1992

Monoclonal anti-idiotype antibody therapy of B-cell lymphoma: the addition of a short course of chemotherapy does not interfere with the antitumor effect nor prevent the emergence of idiotype-negative variant cells.

The Ig idiotype of B-cell lymphoma can be used as a tumor-specific target. Prior trials with monoclonal anti-idiotype antibodies alone and combined with alpha-interferon have shown significant antitumor activity. In some patients, idiotype-negative tumors emerged after treatment. In this trial, patients with relapsed non-Hodgkin's lymphoma were treated with two identical courses of monoclonal anti-idiotype anti-body therapy. Concurrent with the second course, at a time when idiotype-negative cells were suspected to be proliferating, a pulse dose of chlorambucil was administered. Tumor biopsies obtained before the first and second courses of treatment and at relapse were analyzed for idiotype expression and proliferation. Thirteen patients received 24 courses of antibody with minimal toxicity. Eleven had tumor regression, with 1 complete remission, 8 partial remissions, and 2 minor remissions, with freedom from progression lasting a median of 7 months in responding patients. Idiotype-negative tumor cells appeared in some relapse specimens despite the use of chlorambucil. In retrospect, this was not surprising because there was no increase in the proliferative rate of these tumors at the time the drug was used. Anti-idiotype antibodies continue to demonstrate antitumor activity against B-cell lymphoma with minimal toxicity. The mechanism of the effect is presumed to involve both direct antiproliferative effects of the antibody on the tumor cells as well as indirect, more long-lasting effects on the host. The addition of a mild chemotherapeutic agent in the dose and schedule used here to the second cycle of antibody therapy did not interfere with the antitumor effect, nor did it decrease the emergence of idiotype-negative cells.

Adult↗
PubMed1992

Rates of cyanide binding to the catalytic intermediates of mammalian cytochrome c oxidase, and the effects of cytochrome c and poly(L-lysine).

Rate constants of cyanide binding to 'fast' oxidase have been measured in the fully-oxidised (O), peroxy (P) and ferryl (F) states at pH 8.0. Values of 2.2, 8 and 10 M-1 s-1, respectively, were obtained. Thus, none of these states appears to exhibit a rate that would identify it as the species responsible for the extremely rapid cyanide binding observed during turnover. On the other hand, with 'oxidised' enzyme as prepared, containing a very small fraction of one-electron-reduced (E state) oxidase, a corresponding fraction of enzyme exhibited spectral changes consistent with cyanide binding with a rate constant in excess of 10(4) M-1 s-1. Evidence is presented suggesting that mediation of electron transfer from one-electron-reduced, cyanide-liganded enzyme to free, ferric oxidase, rather than a global protein conformational change of the enzyme, is responsible for the greatly enhanced cyanide binding rates seen in the presence of cytochrome c or poly(L-lysine). Inter-oxidase electron exchange in 'oxidised' enzyme can result in a complicated dependence of the binding rate on cyanide concentration. We have demonstrated that this may give rise to a saturation of the rate of cyanide binding.

Animals↗
PubMed1992

Improved stenosis geometry by quantitative coronary arteriography after vigorous risk factor modification.

This study is a randomized, controlled, blinded, arteriographic trial to determine the effects of a low-cholesterol, low-fat, vegetarian diet, stress management and moderate aerobic exercise on geometric dimensions, shape and fluid dynamic characteristics of coronary artery stenoses in humans. Complex changes of different primary stenosis dimensions in opposite directions or to different degrees cause stenosis shape change with profound effects on fluid dynamic severity, not accounted for by simple percent narrowing. Accordingly, all stenosis dimensions were analyzed, including proximal, minimal, distal diameter, integrated length, exit angles and exit effects, determining stenosis shape and a single integrated measure of stenosis severity, stenosis flow reserve reflecting functional severity. In the control group, complex shape change and a stenosis-molding characteristic of statistically significant progressing severity occurred with worsening of stenosis flow reserve. In the treated group, complex shape change and stenosis molding characteristic of significant regressing severity was observed with improved stenosis flow reserve, thereby documenting the multidimensional characteristics of regressing coronary artery disease in humans.

Adult↗
PubMed1992

The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid.

(+)-Catechin inhibited the copper-catalysed oxidation of human low density lipoprotein (LDL) in a dose-dependent manner with complete inhibition at 20 micrograms/mL. The flavonoid at a concentration of 50 micrograms/mL also inhibited oxidation of LDL induced by the mouse transformed macrophage J774, human monocyte-derived macrophages and vascular endothelial cells isolated from human umbilical cords. LDL modified by copper-catalysed or cell-induced oxidation was endocytosed and degraded by human macrophages at a much greater rate than native LDL. LDL reisolated from copper or cell incubations in the presence of (+)-catechin was endocytosed and degraded at rates similar to native LDL. (+)-Catechin appeared to inhibit the uptake and degradation by macrophages of cell-modified LDL. The actions of (+)-catechin on cell-induced oxidation of LDL are consistent with the ability of flavonoids of similar structure to inhibit lipoxygenases and with a role for lipoxygenases in cell-induced modification of LDL in vivo.

Animals↗
PubMed1992

To stay or not to stay: are fears about shorter postnatal hospital stays justified?

Common concerns raised during a Ministerial Review of Birthing Services in Victoria, Australia about the potential detrimental effects of shorter hospital stays after birth were examined in a study of women's actual experiences of and opinions about their hospital stays. Just under one in four women left hospital within five days of the birth, with the greater majority staying five days or more. Satisfaction with length of stay was high in the sample, with 82% of women feeling their stay had been about right, 11% feeling it had been too long and only 7% of women feeling their stay had been too short. A number of the concerns about the consequences of shorter lengths of stay were not borne out. Women who left hospital earlier than the traditional 5-7 day stay were not less likely to breast feed, nor were they more likely to be depressed 8-9 months after the birth. They were also much more likely to feel confident about looking after their baby when they went home than women who stayed five days or more. Implications for further research and for policy development concerning length of stay are considered.

Adult↗
PubMed1992

Organizational planning: a program evaluation survey of AACE members.

The Long Range Planning Committee of the American Association for Cancer Education (AACE) has completed a comprehensive survey of AACE members. The survey was distributed in July and August 1989 to 592 AACE members, and 360 (61%) returned completed forms. The respondents did not differ markedly from the membership as a whole on selected member characteristics. Survey questions addressed the following aspects of the AACE: Annual Meeting, Special Interest Sections, Liaison Relationships, Journal of Cancer Education (JCE), and Communications. Results showed that the AACE is healthy and responsive to the needs of its members. Several areas needing attention were indicated, but no significant concerns were noted.

Communication↗
PubMed1992

Interleukin-5 increases the expression of alkaline phosphatase activity in murine B lymphocytes.

Interleukin-5 (IL-5) was shown to enhance, in a dose-dependent fashion, the expression of alkaline phosphatase (APase) activity in splenic B cells stimulated with dextran sulphate (DXS). The potentiating effect of IL-5 was still more evident when assayed in large B cells than in small resting B cells, whereas IL-2, IL-4 and IL-6 were devoid of activity. Concomitant with increased APase expression, cell-cycle analysis by flow cytometry showed that large B cells in the early G1 phase were stimulated by IL-5, in conjunction with DXS, to enter G1B and to progress further through S and G2/M. A phosphorylation-dephosphorylation pathway could, thus, be involved in IL-5 transmembrane signalling.

Adenosine Triphosphatases↗
PubMed1991

Evidence for a functional link between profilin and CAP in the yeast S. cerevisiae.

CAP is a component of the S. cerevisiae adenylyl cyclase complex. The N-terminal domain is required for cellular RAS responsiveness. Loss of the C-terminal domain is associated with morphological and nutritional defects. Here we report that cap- cells bud randomly and are defective in actin distribution. The morphological and nutritional defects associated with loss of the CAP C-terminal domain are suppressed by over-expression of PFY, the gene encoding profilin, an actin- and polyphosphoinositide-binding protein. The phenotype of cells lacking PFY resembles that of cells lacking the CAP C-terminal domain. Study of mutated yeast profilins and profilins from Acanthamoeba suggests that the ability of profilin to suppress cap- cells is dependent upon a property other than, or in addition to, its ability to bind actin. This property may be its ability to bind polyphosphoinositides. We propose that CAP and profilin provide a link between growth signals and remodeling of the cellular cytoskeleton.

Actins↗
PubMed1991

AIDS research at NIH.

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Acquired Immunodeficiency Syndrome↗