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Biomedical subjects

S Cooper

Publications and source records attributed to S Cooper.

At least 253 records · Page 14Linked to original sources
PubMed1990

Relationship between the acceptor/donor radioactivity ratio and cross-linking in bacterial peptidoglycan: application to surface synthesis during the division cycle.

The relationship between the experimental measurement of the cross-linking of bacterial peptidoglycan and the mode of its insertion is analyzed. The cross-linking value, in practice and in theory, is independent of the pattern of strand insertion. Since the measure of the mode or pattern of insertion is the acceptor/donor radioactivity ratio (ADRR), no correction need be made for the ADRR. The measurement of cross-linking using radioactivity is independent of the labeling time, the specific activity of the label, and the mode of strand insertion. It is not concluded, however, that cross-linking does increase during the division cycle.

Bacteria↗
PubMed1990

Clinical study of a C31G containing mouthrinse: effect on salivary microorganisms.

In vitro studies have demonstrated the antiplaque properties of C31G, a potent broad spectrum antimicrobial agent consisting of an equimolar mixture of alkyl dimethyl glycine and alkyl dimethyl amine oxide, buffered with citric acid. In this initial clinical study, C31G at concentrations of 0.05%, 0.1%, 0.2% and 0.5%. Listerine, and placebo were tested in a complete crossover design. Twelve subjects were evaluated, with a minimum of 2 days between treatments. Parameters monitored were salivary bacterial counts and saliva glycolysis. The 0.5% and 0.2% C31G mouthrinses significantly reduced total bacterial counts in saliva samples obtained up to and including three hours after rinsing, compared with counts obtained prerinsing or after placebo rinsing. Both 0.5%, and 0.2% C31G significantly inhibited glycolysis of salivary bacteria for up to 6 hours postrinsing, compared with pH values obtained prerinsing. 0.1% and 0.05% C31G exhibited little or no effect in either assay. Listerine showed a significant reduction in bacterial counts for up to 1 hour postrinsing, compared with prerinse counts, but the effect was less sustained. Listerine showed no significant inhibition of glycolysis at any time point. No tooth staining or altered taste sensation was noted with either product.

Adult↗
PubMed1990

Antibodies to denatured type II collagen in rheumatoid arthritis: negative association with IgM rheumatoid factor.

Serum samples from 129 patients with definite or classic rheumatoid arthritis (RA) were assayed by ELISA for antibodies to denatured bovine type II collagen (dII). All patients had active disease at the time of serum sampling. Anti-dII antibodies were found in 18 (14%) of 129 patients (95% confidence intervals: 8-20%). The only clinical or laboratory feature associated with the presence of anti-dII antibodies was seronegativity for IgM rheumatoid factor (IgM RF): 6 (37.5%) of 16 seronegative patients had anti-dII antibodies vs 12 (10.6%) of the 113 seropositive patients (OR = 5, p less than 0.01). There were no associations of anti-dII antibodies with age, sex, race, disease activity, disease duration, functional class, or the presence of HLA-DR1, DR4, or DQw3 in these patients. Antibodies to type II collagen may have a pathophysiologic role in RA, especially in patients seronegative for RF.

Adult↗
PubMed1989

Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte/macrophage progenitor cells.

Two recently identified and purified murine macrophage inflammatory proteins MIP-1 and MIP-2 were tested in vitro both alone, and in combination with purified recombinant (r) murine (mu) GM-CSF, natural (n)muCSF-1, or rhuman (hu)G-CSF, for effects on mouse marrow CFU-GM, in combination with erythropoietin for effects on mouse marrow BFU-E, and in combination with rhuGM-CSF or rhuG-CSF for effects on human marrow CFU-GM. MIP-1 and MIP-2 did not stimulate, but did enhance by up to threefold, colony formation of mouse CFU-GM co-stimulated by rmuGM-CSF and nmuCSF-1, but not by rhuG-CSF, in the absence or presence of serum. MIP-1 and MIP-2 were maximally active at concentrations greater than or equal to 100 ng/ml and the actions appeared to be initiated during the DNA synthetic portion of the cell cycle. Neither MIP-1 nor MIP-2 at up to 1 microgram/ml had any effect on mouse BFU-E, in the absence or presence of erythropoietin. Both MIP-1 and MIP-2 had direct acting effects on purified mouse CFU-GM. The cloning efficiency of 200 purified cells plated with 50 U muCSF-1 was 82% with and 43% without MIP; the cloning efficiency with 50 U rmuGM-CSF was 65% with and 35% without MIP. MIP effects were not mimicked by bacterial LPS, rhuIL-1 alpha, rhuIL-6, or rmuIL-4, and were neutralized by their respective specific antibodies. MIP-1 and MIP-2 also enhanced endogenously stimulated and rhuGM-CSF-, but not rhuG-CSF-, stimulated colony formation by human marrow CFU-GM. These results demonstrate a new role for MIP-1 and MIP-2 in vitro as myelopoietic enhancing activities for CFU-GM.

Animals↗
PubMed1989

Diethyldithiocarbamate and disulfiram inhibit MPP+ and dopamine uptake by striatal synaptosomes.

Diethyldithiocarbamate (DDC) was found to inhibit the uptake of both dopamine and 1-methyl-4-phenyl-pyridinium ion (MPP+, the putative toxic metabolite of the neurotoxicant MPTP) by striatal synaptosomes. Disulfiram, the corresponding disulfide of DDC, was effective at concentrations 1,000 times lower (10(-6) vs. 10(-3) M). Disulfiram, but not DDC, reacted very efficiently with synaptosomal protein thiols; both DDC- and disulfiram-induced uptake inhibition could be reversed by the thiol-reducing agent dithiothreitol. Two other thiol-reactive compounds, N-ethylmaleimide (NEM) and p-hydroxymercuribenzoate (PMB), also impaired the uptake of MPP+ by striatal synaptosomes. PMB, which does not cross membranes, was even more potent than the lipophilic NEM in blocking MPP+ uptake. These results suggest that (1) the effect of DDC may be mediated by disulfiram, (2) the uptake of MPP+ and dopamine by striatal synaptosomes is dependent on the redox state of protein thiols, and (3) these protein thiols are located at the outer surface of synaptosomal membranes.

1-Methyl-4-phenylpyridinium↗
PubMed1989

Effect in vivo of multiple injections of purified murine and recombinant human macrophage colony-stimulating factor to mice.

Hematopoietic efficacy in vivo of multiple injections of purified murine L-cell and recombinant human macrophage colony-stimulating factors (M-CSF; specific activity, greater than 2 x 10(7) units/mg) was assessed in mice. Injections i.v. of sterile saline or 20,000 units of M-CSF were administered once (at 0 h), twice (at 0 and 12 h), or three times (at 0, 12, and 24 h) to C57BL/6 x DBA/2 F1 mice. Numbers and cycling rates of marrow and spleen granulocyte-macrophage, erythroid, and multipotential progenitor cells were assessed 32-36 h after the first injection. Marrow, spleen, and peripheral blood cellularity was assessed at intervals of up to 105 h. Progenitor cell cycling rates were significantly increased after one and two injections of M-CSF but were reduced to a slow or noncycling state after three injections. For marrow cells, the third injection resulted in a significant suppression of hematopoietic progenitor cell cycling compared to the control group. No significant changes were noted for number of progenitors per femur or spleen, for marrow, spleen, or peripheral blood cellularity, or for differential cell counts in these organs after any of the M-CSF treatment schedules. Suppression of progenitor cell proliferation noted after three injections of M-CSF may at least partially explain why repeated injections of 20,000 units of M-CSF fails to increase bone marrow, spleen, or blood cellularity even though one injection of M-CSF increases cycling rates of the hematopoietic progenitors.

Animals↗
PubMed1989

A Markov transition model in the analysis of the immune response.

A method for the analysis of repeated measures of immune response is given. Typically the reactions of response to stimulus do not occur at the same time for all experimental units so that regression models are inappropriate for this type of data. Instead Markov transition models are suggested and procedures given for testing differences among response patterns.

Immunity↗
PubMed1989

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells.

The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution. Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability. We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation. First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service. Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3. The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1.077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells. Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater. The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution.

Blood Preservation↗
PubMed1989

The relationship between thought disorder and psychotic symptoms in borderline personality disorder.

Often patients with personality and affective disorder are troubled by psychotic and psychotic-like symptoms. Predicting a course that includes such symptoms, and subsequently adjusting treatment to take into consideration the added difficulties presented by psychosis, is clinically important. In the current study, a measure of thought disorder, the Thought Disorder Index (TDI), significantly predicted prospective psychotic and psychotic-like symptoms in a sample of 49 personality and affective disorder patients. Multiple regressions demonstrated that the TDI had predictive value above and beyond that of a clinical interview. The high prevalence of psychotic symptoms was most striking in patients with borderline personality disorder.

Adult↗
PubMed1989

Isolation and characterization of a multipotent clone of human embryonal carcinoma cells.

Histopathological studies suggest that the stem cells of human teratomas may be classified into two major categories: nullipotent stem cells, and multipotent stem cells, capable both of self-renewal and differentiation into a wide range of somatic and extraembryonic cell types. We have isolated a multipotent stem cell clone from the human teratoma cell line GCT 27, and compared its properties to a nullipotent clone derived from the same strain. The multipotent clone GCT 27 X-1 gave rise to colonies of mixed cell morphology in vitro. Analysis of cell surface, cytostructural and extracellular matrix markers in GCT 27 X-1 cells showed that the stem cells of this line were very similar in phenotype to nullipotent cells. The two cell clones were predominantly hypotriploid, and contained several marker chromosomes in common. GCT 27 X-1 was feeder-cell-dependent for continuous growth in vitro; removal of the feeder layer resulted in differentiation of the stem cells into a variety of cell types, some with characteristics of extraembryonic endoderm, others showing neuronal properties. When transplanted into nude mice, GCT 27 X-1 cells gave rise to teratocarcinomas containing embryonal carcinoma stem cells, and many other cell types: yolk sac carcinoma cells; cells producing alphafetoprotein or human chorionic gonadotrophin; glandular, columnar, cuboidal, and squamous epithelium; primitive mesenchyme and cartilage; neuroectodermal cells. Nullipotent GCT 27 C-1 cells could form colonies in the absence of feeder layers, but multipotent GCT 27 X-1 cells could not. While a range of known growth factors and related substances failed to substitute for feeder layers in supporting the growth of GCT 27 X-1 stem cells, supernatants from yolk sac carcinoma cell line GCT 44 could partially replace the feeder cell requirement. Thus, the results revealed a basic difference in growth control between these multipotent and nullipotent human embryonal carcinoma cells, and suggested a possible paracrine regulatory pathway between multipotent stem cells and yolk sac carcinoma cells.

Animals↗
PubMed1989

The effects of oxidizing species derived from molecular oxygen on the proliferation in vitro of human granulocyte-macrophage progenitor cells.

In order to better understand the enhancing effects of lowered oxygen (O2) tension on the growth in vitro of granulocyte-macrophage progenitor cells (CFU-GM), the effects of oxidizing species derived from molecular O2 were assessed on CFU-GM. Low density or nonadherent low density normal human bone marrow cells were plated at ambient (20%) or lowered (5%) O2 tension in the presence of a source of colony stimulating factors, and in the absence or presence of superoxide dismutase, catalase, glucose oxidase or horseradish peroxidase, alone or in various combinations. Enhanced colony and cluster formation of CFU-GM was noted when low density cells were grown at 5% O2, or when cells were grown at 20% O2 in the presence of superoxide dismutase or glucose oxidase. Both of these enzymes are capable of generating hydrogen peroxide (H2O2), although by different mechanisms. Low concentrations of glucose oxidase resulted in increased formation of colonies and clusters, but higher concentrations of glucose oxidase were inhibitory. Catalase, which converts H2O2 to H2O, had no effect by itself on cells growing at 20% O2, but it eliminated the superoxide dismutase and glucose oxidase enhancing effects. Catalase decreased colony formation of cells grown at 5% O2. Removal of adherent cells ablated the growth-enhancing effects noted at lowered (5%) O2 tension and also the superoxide dismutase and catalase effects at 20% or 5% O2. Horseradish peroxidase, which converts H2O2 to a more toxic oxidant, hypochlorite, had a suppressive effect on colony and cluster numbers and at 20% O2 converted the glucose oxidase effects from stimulatory to inhibitory. The results suggest that adherent cells and low concentrations of H2O2 may mediate growth-enhancing effects of CFU-GM seen at lowered (5%) O2 tension.

Bone Marrow Cells↗
PubMed1989

Cell cycle status of erythroid (BFU-E) progenitor cells from the bone marrows of patients on a clinical trial with purified recombinant human granulocyte-macrophage colony-stimulating factor.

Human Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is active in vitro as a Burst Promoting Activity (BPA) for human erythroid (BFU-E) progenitor cells. In order to evaluate the effectiveness of GM-CSF as a proliferation-inducing stimulus for BFU-E in vivo, bone marrow cells from patients on a phase I/II clinical trial with recombinant human (rh) GM-CSF, were assessed in vitro for effects on the cycling status of BFU-E. Prior to treatment, BFU-E from marrows of the majority of these patients were in a slowly cycling state. Administration of rhGM-CSF to the patients enhanced BFU-E proliferation, and cessation of treatment with rhGM-CSF resulted in BFU-E returning to a slowly cycling state. Similar results were noted for CFU-GM. This study demonstrates that rhGM-CSF has proliferation-inducing activity for BFU-E in vivo, substantiating the in vitro BPA activity previously noted for GM-CSF, although it is not possible from the present studies in vivo to determine if this effect on BFU-E is directly or indirectly mediated.

Bone Marrow↗
PubMed1989

Suppressive effects in vivo of purified recombinant human H-subunit (acidic) ferritin on murine myelopoiesis.

Purified recombinant human heavy-chain (acidic) ferritin (rHF) was assessed in vivo in mice for effects on the proliferation (percentage of cells in S-phase) and absolute numbers of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells in the femur and spleen and on the nucleated cells in the marrow, spleen, and blood. rHF significantly decreased cycling rates and absolute numbers of marrow and splenic hematopoietic progenitors and marrow and blood nucleated cellularity. These effects were apparent in BDF1, C3H/Hej and DBA/2 mice and were dose dependent, time related, and reversible. Suppressive effects were noted within three hours for progenitor cell cycling, within 24 hours for progenitor cell numbers, and within 48 hours for circulating neutrophils. Additionally, hematopoietic progenitor cells in DBA/2 mice infected with the polycythemia-inducing strain of the Friend virus complex (FVC-P) were insensitive to the in vivo administration of rHF. These studies demonstrate activity of rHF in vivo on myelopoiesis of normal but not FVC-P-infected mice. Since rHF suppresses hematopoietic progenitor cell proliferation from normal donors in vitro and from normal mice in vitro and in vivo but does not suppress progenitor cells from patients with leukemia in vitro or from mice with FVC-P-infection in vitro or in vivo, rHF may be useful as a candidate adjunct molecule for the protection of normal hematopoietic progenitor cells during chemotherapy.

Animals↗
PubMed1988

The continuum model and c-myc synthesis during the division cycle.

Discordant results on the synthesis of c-myc gene products during the division cycle are reanalyzed and shown to be understood in light of the continuum model. It is proposed that there is no G1-phase dependence of c-myc synthesis. The large amount of data supporting G1-specific syntheses and a G(0) state must be re-examined.

Animals↗
PubMed1988

Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions.

Purified recombinant human B cell growth factor-1/IL-4 was evaluated, alone and in combination, with purified preparations of recombinant human (rhu) CSF or erythropoietin (Epo) for effects on colony formation by human bone marrow CFU-GM progenitor cells (GM) and burst forming unit-E progenitor cells. rhu IL-4 synergized with rhu G-CSF to enhance granulocyte colony formation, but had no effect on CFU-GM colony formation stimulated by rhu GM-CSF, rhu IL-3, or rhu CSF-1. Rhu IL-4 synergized with Epo to enhance BFU-E colony formation equal to that of Epo plus either rhu IL-3, rhu GM-CSF, or rhu G-CSF. Removal of adherent cells and T lymphocytes did not influence the synergistic activities of rhu IL-4. Rmu IL-4, synergized with rhu G-CSF, but not with rmu GM-CSF, rmu IL-3, or natural mu CSF-1, to enhance CFU-GM (mainly granulocyte) colony numbers by a greater than 90% pure preparation of murine CFU-GM. Also, rhu IL-4 at low concentrations enhanced release of CSF and at higher concentrations the release also of suppressor molecules from human monocytes and PHA-stimulated human T lymphocytes. Use of specific CSF antibodies suggested that rhu IL-4 was enhancing the release of G-CSF and CSF-1 from monocytes and the release of GM-CSF and possibly G-CSF from PHA-stimulated T lymphocytes. Use of antibodies for TNF-alpha, IFN-gamma, or TNF-beta as well as measurement of TNF and IFN titers suggested that the suppressor molecule(s) released from monocytes were acting with TNF-alpha and those released from PHA-stimulated T lymphocytes were acting with IFN-gamma. These results implicate B cell growth factor-1/IL-4 as a synergistic activity for hematopoietic progenitors and suggest that the actions can be on both progenitor and accessory cells.

Animals↗