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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 325 records · Page 18Linked to original sources
PubMed1987

Differences of T-cell activation by the anti-CD3 antibodies Leu4 and BMA030.

Two anti-CD3 antibodies and their Fab/F(ab')2 fragments were compared with regard to their requirement for secondary signals and generations of intracellular messengers. The anti-CD3 antibody BMA030 was found to require monocyte contact to elicit T-cell mitogenesis. Cross-linking by plastic-bound goat anti-mouse antibodies (panning) failed to activate T cells, even in the presence of recombinant IL-1 or IL-2. In contrast, crosslinking of the anti-CD3 antibody Leu4 or Leu4 fragments was mitogenic in monocyte-free cultures. Measurements of intracellular Ca2+ ([Ca2+]i) and generation of inositol phosphates revealed that binding (+/- panning) of BMA030, Leu4, and their F(ab')2 fragments generated similar amounts of intracellular messengers and thus failed to explain the different responsiveness to passive crosslinking. Since the generation of these messengers was not necessarily followed by proliferation but was always observed when mitogenesis occurred, we conclude that the elevation of [Ca2+]i and the production of inositol phosphates are required but not sufficient to trigger mitogenesis.

Adult↗
PubMed1987

In vitro secretion of human chorionic gonadotrophin by bladder tumour cells.

Human chorionic gonadotrophin (hCG) and alphafetoprotein (AFP) were measured in culture media from a panel of 29 cell lines including 9 bladder carcinomas, 5 'normal' bladder epithelia, 10 germ cell tumours, and 5 miscellaneous tumours and 'normal' cell lines. In 7 of the 9 bladder carcinomas and 4 of the 5 'normal' bladder epithelia, the media contained hCG at levels ranging from between 34 and 3,600 IU l(-1). All other cell lines, including the 10 germ cell tumour lines gave negative results for hCG. These findings indicate that in vitro secretion of hCG is a common feature of normal and neoplastic bladder transitional epithelia, and support the hypothesis that parts of the genito-urinary epithelium have a potential for hCG production.

Cell Line↗
PubMed1987

Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells.

Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and, ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat alveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of approximately 4 kilobases. We conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor.

Animals↗
PubMed1987

Alloantibody responses in multiply transfused sickle cell patients.

Fifty-six adult and 15 pediatric black patients with sickle cell disease were studied to determine their antibody responses to repeated transfusions of red cells. Red cell antibodies were determined retrospectively; anti-lymphocyte antibodies (class I and II) were determined on the single, most recently drawn blood sample. All adults were HLA-A, B, C, DR and DQ typed. Ten percent of the individuals with less than 50 transfusions, but greater than 50% with 100 transfusions or more, had red cell antibodies. The percentage of patients producing anti-red cell antibodies increased consistently with the number of transfusions (p = 0.0062). Women were more likely to become sensitized to red cell antigens than men (p = 0.008), and nulliparous women more likely than multiparous women. Children were also sensitized to red cell antigens (20%), and to a high degree to lymphocyte antigens (73%). No HLA association was found with increased propensity to red cell sensitization. A weak association of HLA DR5 and DR7 with failure to become sensitized to lymphocyte alloantigens was observed, but did not reach statistical significance. Our results suggest that, while genetic factors influencing transfusion response almost certainly exist, other factors such as number of transfusions, age, sex and parity need to be examined to provide accurate projections of risk in chronic transfusion.

Age Factors↗
PubMed1987

Effect of schistosome-derived inhibitory factor on the cell cycle of T lymphocytes.

A schistosome-derived inhibitory factor (SDIF) with immunosuppressive properties has been investigated for its effect on human T cell proliferation. We show here that SDIF has no effect on the process of lymphocyte activation because peripheral blood leukocytes (PBL) stimulated with lectin in the presence of SDIF increased normally their RNA content and showed normal acquisition of interleukin 2 (IL-2) and transferrin receptors. IL-2 production was not altered by SDIF but utilization of IL-2 was decreased, suggesting that SDIF blocked cells before or in the early s phase. Jurkat T cell line cells physically enriched for G1 cells were also more susceptible to SDIF inhibition. On the contrary, normal PBL or Jurkat cells which were already in the s phase were no more inhibited by SDIF. While SDIF has no effect on T lymphocyte activation and on production of regulatory lymphokines it selectively blocks T cell proliferation at G1 transition of the cell cycle.

Cell Cycle↗
PubMed1987

An endothelial cell growth factor derived from human lung carcinoma cells grown in serum-free medium.

A factor that stimulates the proliferation of human umbilical vein endothelial cells has been shown to be present in serum-free medium conditioned by the prior growth of a cell line (1PT) derived from a poorly differentiated bronchial carcinoma. Preliminary characterization of this factor has revealed that it is a heat-labile, acid-stable proteinaceous material, the activity of which is not diminished by treatment with a reducing agent. In its partially purified state it has been shown to be anionic and to be associated with material exhibiting a broad molecular weight range of 35 X 10(3) to 100 X 10(3). It does not bind strongly to heparin-Sepharose and its mitogenic effect on endothelial cells is not potentiated by heparin. These properties suggest that this factor may differ from other previously described tumour-derived endothelial mitogens.

Carcinoma, Bronchogenic↗
PubMed1987

Suppression of tumorigenicity mediated by 5-azacytidine and associated with increased chromosome number.

5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 micrograms 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68-94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell's tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell's chromosome complement.

Animals↗
PubMed1986

Interference of a C3-fragment preparation with IL 2-dependent proliferation.

A C3-fragment preparation (C3-FP) was studied for its ability to regulate human peripheral blood lymphocyte activation. It was found that very low concentrations of this low m.w. fraction, which was free of C3a, inhibited the PHA-induced lymphocyte proliferation without any cytotoxicity. Cytofluorometric analysis showed that C3-FP did not influence the transition of T cells from the G0 to the G1a phase of the cell cycle. However, the IL 2-dependent transition from the G1a to the G1b phase of the cell cycle was effectively blocked. Addition of exogenous IL 2 did not release cells arrested in the G1a phase. Furthermore, neither IL 2 production nor IL 2 receptor formation was inhibited by C3-FP, and binding of IL 2 to its receptor was unaltered. It was found that only IL 2-dependent cell lines were inhibited in their proliferation; all other tested cell lines were unaffected by C3-FP. Our findings suggest that cleaved products of C3 may inhibit IL 2-dependent lymphocyte proliferation at a stage where the IL 2 signal is required for initiation of proliferation.

Complement C3↗
PubMed1986

Different effects of IL-2 addition or antibody crosslinking on T-cell subset stimulation by CD3 antibodies.

The effect of exogenous recombinant interleukin-2 (IL-2) or of antibody crosslinking on the activation of human T-cell subsets by IgG2a (OKT3/BMA030), IgG1 (Leu4 and UCHT1), or IgG2b (BMA031) anti-T3 antibodies (CD3) was investigated. In so-called nonresponder cultures as well as in monocyte-depleted cell cultures addition of IL-2 increased the CD3-induced activation and proliferation of T4 and T8 cell subsets. Relatively more T8 than T4 cells were stimulated by antibody binding and IL-2. Crosslinking the cell-bound CD3 antibodies by plastic bound goat anti-mouse antibodies activated both T-cell subsets optimally and increased the IL-2 production of the IgG1-CD3 stimulated cultures. The data show that T cells (T8 greater than T4) can be stimulated by CD3 antibody binding and IL-2, but that crosslinking the cell-bound CD3 antibodies is crucial for optimal T4 cell stimulation and IL-2 production.

Adult↗
PubMed1986

In vitro antimicrobial activity of six pulp-capping agents.

The antimicrobial activity of six commonly used pulp-capping agents was compared to reagent Ca(OH)2 by means of an in vitro microbiologic assay. Microbial samples were collected from deep carious lesions in each of twelve teeth and plated onto T-soy blood agar. Uniform disks of each pulp-capping agent were pressed slightly below the surface of each agar dish, and zones of bacterial inhibition were measured at 24 hours to the nearest 0.1 mm. All agents, including IRM, demonstrated significantly more antimicrobial activity than reagent Ca(OH)2 with the exception of Pulpdent. This tends to indicate that the antibacterial properties associated with these capping compounds are not entirely due to the high pH associated with Ca(OH)2.

Bacteria↗
PubMed1986

Mesial prefrontal cortical lesions and timidity in rats. II. Reactivity to novel stimuli.

An earlier set of experiments suggested that mesial prefrontal cortical (MFC) lesions in rats enhanced timidity. It was uncertain whether this increased timidity was a general phenomenon, or was restricted to fear of bright, open spaces. The experiments reported here measured behavioral reactivity to a variety of stimuli, under situations where light/dark differences were minimized. It was found that MFC rats were slowed in leaving an open field to enter a small box. In the open field, MFC subjects showed signs of enhanced reactivity, but only when the field was novel and the subjects unhandled. When allowed to choose between four alleys containing varying stimuli, brain-damaged rats avoided novel objects and complex stimuli, but spent more time than controls in contact with other rats in the apparatus. In a test of food neophobia, MFC subjects were not neophobic in a familiar test environment, but did avoid the experimenter more than controls. Finally, duration of barbiturate anesthesia was shortened by MFC lesions, but only under conditions of high novelty. It is concluded that MFC lesions produce a timidity which is not restricted to photophobia.

Animals↗
PubMed1986

Factors affecting the reproducibility of a spectrofluorimetric assay for the enumeration of human venous endothelium in culture.

In an EDTA/Hoechst 33258 assay system, a linear increase in fluorescence with increase in cell number between 2 X 10(3) and 1 X 10(5) was obtained if a dye concentration of 800 ng/ml was used. For a given number of cells, the enhancement of fluorescence was found to be greater than that of a theoretically equivalent of DNA. A standard curve for the assay was derived by plotting enhancement of fluorescence against cell number. The effect of storage on the fluorescence of intact monolayers, cellular or commercial DNA, or dye-DNA complexes made it essential that the assay was carried out on fresh samples.

Bisbenzimidazole↗
PubMed1986

Different T cell subset stimulation by IgG1 or IgG2a anti-T3 antibodies.

In so-called responder cell cultures--able to be stimulated by mouse IgG1 anti-T3 antibodies (IgG1-CD3)--the proliferation, IL 2 secretion and IL 2 receptor expression were lower in IgG1-CD3 than in IgG2a-CD3-stimulated cultures. Using a double-fluorescent technique, we found that IgG1-CD3 antibodies stimulate fewer T4 cells, but the same amount of T8 cells, than IgG2a-CD3 antibodies. The suboptimal T4 cells stimulation could be enhanced by adding exogenous IL 2 or by crosslinking the IgG1-CD3 antibodies by plastic-bound goat anti mouse IgG antibodies. Following antibody-mediated crosslinking, high IL 2 levels could also be found in IgG1-CD3-stimulated cultures. We conclude that CD3 antibodies of the mouse IgG1 isotype stimulate fewer T4 cells, due to insufficient crosslinking by monocytes and that T3 structure crosslinking is essential for optimal IL 2 production and secretion.

Adult↗
PubMed1986

Segregation analyses and gene-centromere distances in zebrafish.

The gol-1, gol-2, alb-1 and spa-1 mutations affect pigment pattern in the zebrafish. We show here that these loci are unlinked to each other. In addition, gene-centromere distances were determined for these loci by analysis of half-tetrads obtained by the inhibition of the second meiotic division. The fractions of tetratype (second-division segregation) tetrads range from 0.24 (spa-1) to 0.89 (gol-1). The observation of greater than 0.67 second-division segregation indicates that the zebrafish has high chiasma interference.

Animals↗
PubMed1986

Cost-effectiveness of fine needle biopsy of the breast.

Although fine needle aspiration (FNA) biopsy of the breast has been shown to be a safe and accurate technique, many surgeons question whether it is reliable enough to replace excisional biopsy. If FNA biopsy is followed by excisional biopsy for confirmation, it would seem that the cost of diagnostic work-up would be increased. In this study, however, the authors show that the major economic benefit of FNA biopsy is not that it replaces excisional biopsy, but that it allows the surgeon to triage which patients should have a 1-stage inpatient procedure with frozen section and which patients should have an excisional biopsy as an outpatient under local anesthesia. Over the past 2 years, the average cost at the East Carolina University School of Medicine of excisional outpatient biopsy (negative) was +702 +/- 348; inpatient biopsy (negative) was +1410 +/- 262; inpatient 1-stage procedure (positive) was +4135 +/- 361; and outpatient biopsy (positive) followed by inpatient procedure was +4822 +/- 586. The authors' last 100 FNA biopsies were read as 23 positive, three suspicious, 65 negative, and nine insufficient. There were no false-positives and four false-negatives, for a sensitivity of 87%, specificity of 100%, and accuracy of 96%. Using the above figures, it is possible to calculate the cost per case if all 100 cases had been biopsied by the 1-stage inpatient technique (+2227), by the 2-stage outpatient method (+1938), or guided by the FNA biopsy where positive and suspicious readings are followed by an inpatient 1-stage procedure and negative and insufficient readings followed by an outpatient 2-stage procedure (+1759). Since the FNA biopsy costs +75, it resulted in a savings per case of +393 over routine inpatient biopsy and +104 per case over routine outpatient biopsy. Computer analysis revealed that the FNA biopsy would still be economically favorable if the sensitivity of the test fell as low as 37%, the specificity as low as 80%, or if the percentage of cases of cancer in the population biopsied fell as low as 13%. Since FNA biopsy is cost effective even when followed by an excisional or frozen section biopsy for confirmation, it would be safe and reasonable to expand its use to smaller hospitals where the personnel may be initially less experienced with the technique.

Ambulatory Care Facilities↗
PubMed1986

Prediction of amblyopia and squint by means of refraction at age 1 year.

In this series amblyopia, uncorrectable by spectacles and occlusion, was highly likely (48%) if a child had +3.50 or more dioptres of meridional hypermetropia at age 1 year. 45% of children with this refraction also had a squint. All those who remained with severely defective acuity in spite of treatment had either +3.50 or more dioptres of meridional hypermetropia or 4 or more dioptres of meridional myopia at age 1 year. These children were identifiable in the 3.7% of the population at age 1 year who showed high refractive errors. Squint as such was not so accurately predictable. Of those children with squint 71% had less than +3.50 dioptres of meridional hypermetropia at age 1 year--an incidence of 4.4% of the population. Apart from two 'congenital myopes' only 16% of these had residual amblyopia after treatment, and their last known acuity was never less than 6/12. Astigmatism in infancy or later is not significantly associated with squint or amblyopia.

Amblyopia↗