Implementing newly created or revised forms is often difficult and time consuming, and resistance is possible at any stage in the process. However, resistance forces clarity of purpose and dedication. A deliberately planned and carefully managed change process can achieve the goals of the task force and Nursing Administration. The QA nurse analyst is in a strategic position to facilitate this process and achieve a successful outcome within a specific period of time. By involving the head nurses in the initial developmental stage and receiving input from the staff nurses throughout, resistance at the implementation stage will be minimized. Experience with form development illustrates the principle that people affirm change when they have been actively involved in the development process.

Attitude of Health Personnel↗

PubMed1990

Functional cardiac imaging in coronary disease: increased sensitivity of first-pass radionuclide angiography utilizing sequential regional left ventricular early diastolic filling rate images.

In 127 patients, 113 with greater than or equal to 50% coronary artery stenosis (CAD), 14 with normal coronaries, cardiac catheterization and first-pass radionuclide angiography (RNA) utilizing left ventricular (LV) regional ejection fraction, first half systolic LV regional mean transit time and ejection rate images were performed. Additionally, the incremental value of a new technique, sequential regional LV filling rate images focusing on the first third of diastole, was established. Diastolic imaging improved RNA sensitivity from 88% (100/113) to 96% (109/113). Single vessel disease sensitivity increased from 77% (23/30) to 90% (27/30), whereas multivessel disease RNA positivity changed from 93% (77/83) to 99% (82/83). LAD system (LAD/D) sensitivity improved by 24% to 94% (79/84); RCA system (RCA/PDA) sensitivity increased 17% to 84% (59/70); circumflex system (CFX/OM) sensitivity was 83% (67/81), an improvement of 5%. Specificity was well maintained despite the increased sensitivity, as 86% (12/14) of patients with normal coronaries were normal by RNA. Furthermore, in the 113 CAD patients, 81% (84/104) of the vessels with insignificant or no stenosis were normal by RNA. We conclude sequential regional LV diastolic filling images substantially increase RNA sensitivity for CAD, while specificity is satisfactorily maintained.

Coronary Disease↗

PubMed1989

In vitro neoplastic progression of rat tracheal epithelial cells transformed by diverse carcinogens.

Preneoplastic transformants were isolated from primary rat tracheal epithelial cells after treatment with (a) mutagenic concentrations of the alkylating agent N-methyl-N-nitro-N'-nitrosoguanidine, (b) nonmutagenic concentrations of the DNA hypomethylating agent 5-azacytidine, or (c) after arising spontaneously. We have addressed the question of whether preneoplastic transformants induced by different carcinogens differ in their ability to progress to the immortal stage and to become neoplastic. Spontaneous transformants occurred with a very low frequency, and 5-azacytidine induced preneoplastic transformants half as efficiently as N-methyl-N-nitro-N'-nitrosoguanidine. However, no phenotypic differences could be detected between the 70 preneoplastic colonies isolated from the 3 groups; colony size, cell density, and clonogenicity were not statistically different. Clones from all 3 groups became immortal and further progressed to become neoplastic with similar frequencies. The level of expression of the oncogenes H-ras, K-ras, and raf was also similar in all 3 groups. These experiments indicated that there was no difference in the ability of spontaneous transformants or those induced by N-methyl-N-nitro-N'-nitrosoguanidine or 5-azacytidine to progress to become immortal or neoplastic. This suggests that whereas the nature of the carcinogen influenced the frequency of the initial transforming event, progression to the neoplastic stage was independent of the nature of the transforming insult.

Animals↗

PubMed1989

Superoxide-dependent nitroblue tetrazolium reduction and expression of cytochrome b-245 components by human tonsillar B lymphocytes and B cell lines.

EBV-transformed B lymphocyte cell lines can generate superoxide, using an electron transport chain homologous, or even identical, to phagocytic NADPH-oxidase. We searched for normal, not virally transformed, B lymphocytes with analogous properties, using tonsils as the source of B cells. Unseparated tonsillar leukocytes contained cells capable of PMA-triggered superoxide dismutase-inhibitable reduction of nitroblue tetrazolium (NBT+ cells) well in excess of phagocytes (18.9 +/- 6.4% NBT+ cells with 1.3 +/- 0.9% granulocytes and 1.9 +/- 2.3% monocytes/macrophages, n = 8). NBT reduction was also inhibited by diphenylene iodonium, a selective inhibitor of phagocytic NADPH-oxidase. Cross-linking of surface Ig was equally effective as PMA in inducing NBT reduction among tonsillar leukocytes. NBT+ cells co-distributed with B cells on Percoll density gradients and were enriched among purified B cells obtained by SRBC rosetting twice and Sephadex G10 adherence (47.8 +/- 15.2% NBT+ cells among 90.5 +/- 5.5% B cells, 4.8 +/- 5.1% T cells, 1.2 +/- 0.77% monocytes/macrophages, and 0.73 +/- 0.6% granulocytes, n = 10). Further, mAb 7D5, directed against an extracellularly located epitope of the small subunit of cytochrome b-245 of phagocytes, stained the majority of tonsillar B cells (85 +/- 9.2% 7D5+ cells and 91.6 +/- 4.04% B cells, n = 3). Superoxide production, staining with 7D5 antibody, and expression of mRNA for the beta chain of cytochrome b-245 were further analyzed in cell lines. The EBV-BLCL F1 and the Burkitt lymphoma P3HR-1 both carried 7D5-detectable cytochrome b-245 Ag and expressed mRNA for the beta chain of the cytochrome b, both in similar amounts. However, only F1, not P3HR-1, was capable of PMA-triggered superoxide production. These data indicate that also normal nontransformed B lymphocytes possess the capacity to generate superoxide by a system apparently similar to phagocytic NADPH-oxidase, provisionally termed "B cell oxidase." Discrepancies observed in certain B cells and lines between expression of cytochrome b components and stimulus-induced superoxide production may be related to an absence or low level of other oxidase components or of the signal transduction mechanism. Conceivably, production of superoxide and derived reactive oxygen species by B cells may have cytotoxic, immunomodulatory, or mutagenic effects on the B cells themselves or on cells in their immediate vicinity.

Adult↗

PubMed1989

Mouse retroviral sequences acquired by cell lines after passaging through nude mice detected by hybridization of the fms probe pSM3.

The expression of a large RNA transcript, 8.5 to 9.5 kilobases, possibly related to the fms oncogene in mouse, rat, and human tumor cells, has been described in the literature. However, the pSM3 fms probe used to detect this gene transcript contains a significant amount of the pol gene of the Susan McDonough strain of feline sarcoma virus from which it was derived. Using a fms probe which does not contain any viral pol sequences, no such "fms-related" transcripts were detected in cell lines previously reported to express the large transcripts. These cell lines did express a large 9.5-kilobase transcript which hybridized to a probe for murine leukemia virus. Partial sequence analysis of the 9.5-kilobase transcript detected with the pSM3 probe in transformed rat cells indicated sequence homology with AKV murine leukemia virus. Thus, the presence of large RNA transcripts, interpreted by us and others as being related to the oncogene fms, appears to be due to the expression of mouse retroviral sequences which hybridize to the viral pol region contained in the pSM3 fms probe. In the case of rat and human cells, such sequences appear to be acquired after the cells have been passaged in nude mice. These results should serve as a reminder of the important biohazard and data interpretation implications for investigations in which cells transfected with retroviral vector constructs are injected into nude mice, because rescue of the recombinant sequences in these cells could occur following infection by endogenous murine retroviral particles.

Animals↗

PubMed1989

A mutation that changes cell movement and cell fate in the zebrafish embryo.

The study of developmental patterning has been facilitated by the availability of mutations that produce changes in cell fate, in animals such as Caenorhabditis elegans and Drosophila melanogaster. We now describe a zygotic lethal mutation in the zebrafish, Brachydanio rerio, that also changes how particular embryonic cells develop. Severe pattern deficiencies are observed that are restricted to a single body region, the trunk. The mutation may directly affect mesoderm, as somites do not form in the trunk. Head and tail structures, including tail somites, are relatively undisturbed. The earliest detected expression of the mutation is during gastrulation, when movements of mesodermal cells occur incorrectly. We injected prospective trunk mesodermal cells with lineage tracer dye and observed that in mutants these cells may enter a new body region, the tail, and there may express a new fate appropriate for the changed position.

Animals↗

PubMed1989

Lymphokine gene expression related to CD4 T cell subset (CD45R/CDw29) phenotype conversion.

In this study, we investigated whether the phenotype-related differentiation of human 2H4+ (CD45R) naive cells to 2H4- (CDw29) memory CD4 cells corresponded to modulation of interleukin (IL) 2, IL 4, interferon (IFN)-gamma and granulocyte-monocyte colony-stimulating factor (GM-CSF) gene expression, a phenomenon which might correlate to the distinct functional activities of naive cells or memory cells. To mimic in vitro CD4 T cell subset differentiation, freshly isolated 2H4+ and 2H4- CD4 cells were stimulated with the anti-CD3 antibody (Leu-4), expanded in IL 2-containing medium and restimulated with Leu-4 after 7 and 13 days. Absence of monocyte-T cell interaction was compensated by adding monocyte supernatant to the culture medium and by cross-linking the anti-CD3 antibodies with goat anti-mouse antibody coated on culture dishes. It has been previously shown that in vitro stimulated 2H4+ cells acquire CDw29 surface antigens. Measurement of lymphokine gene expression by dot-blot hybridization revealed that although stimulated 2H4+ cells proliferated less than stimulated 2H4- cells, and expressed less actin mRNA, they expressed more IL 2 but less IL 4 and GM-CSF than 2H4- cells. No significant difference was observed between the two subsets for the expression of IFN-gamma. If subsets were restimulated with Leu-4 antibodies, expression of IL 2 was decreased and expression of IL 4 was increased in both subsets; however, the differences among the subsets persisted. They were even more enhanced for IL 2 but less pronounced for GM-CSF. Thus, in spite of phenotype conversion, CD4 T cell subsets maintained a distinct capacity to express IL 2 and IL 4 genes.

Antigens, Differentiation↗

PubMed1989

Controlled clinical trial of adjuvant immunotherapy with BCG and neuraminidase-treated autologous tumour cells in large bowel cancer.

A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.

Adenocarcinoma↗

PubMed1989

Cellular oncogene expression in cell lines derived from tumors produced by transformed rat tracheal epithelial cells.

Five tumor-derived cell lines established from transformed rat tracheal epithelial (RTE) cells were examined for activated oncogenes using the NIH 3T3 assay, and the expression of 11 cellular oncogenes in the transformed cells was quantitated and compared with expression in normal RTE cells. DNA from the tumor-derived cell lines lacked transforming activity, but expression of several oncogenes (fos, abl, Ki-ras, Ha-ras, and p53) was higher in the transformed cells than in normal RTE cells.

Animals↗

PubMed1989

Altered growth factor dependence and transforming growth factor gene expression in transformed rat tracheal epithelial cells.

The role of peptide growth factors in neoplastic progression of transformed rat tracheal epithelial (RTE) cells was assessed by examining growth factor requirements and expression of growth factor and growth factor receptor genes in normal and transformed RTE cells. Neoplastically transformed cell lines showed decreased requirements for bovine pituitary extract, insulin, and epidermal growth factor compared to normal primary RTE cells. Neoplastic RTE cell lines expressed significantly increased levels of transforming growth factor alpha (TGF alpha) RNA and secreted TGF alpha into the media, suggesting an autocrine role for this growth factor. Increased levels of TGF alpha RNA were also observed in the preneoplastic stages of the same cell lines, indicating that increased TGF alpha expression is an early event in the multistage process of neoplastic transformation of RTE cells. TGF beta transcripts were also overexpressed in neoplastically transformed cell lines. Our studies suggest that aberrant expression of growth factors may play an important role in the development and/or maintenance of the transformed phenotype in RTE cells.

Animals↗

PubMed1989

Clonal origins of cells in the pigmented retina of the zebrafish eye.

Mosaic analysis has been used to study the clonal basis of the development of the pigmented retina of the zebrafish, Brachydanio rerio. Zebrafish embryos heterozygous for a recessive mutation at the gol-1 locus were exposed to gamma-irradiation at various developmental stages to create mosaic individuals consisting of wild-type pigmented cells and a clone of pigmentless (golden) cells in the eye. The contribution of individual embryonic cells to the pigmented retina was measured and the total number of cells in the embryo that contributed descendants to this tissue was determined. Until the 32-cell stage, almost every blastomere has some descendants that participate in the formation of the pigmented retina of the zebrafish. During subsequent cell divisions, up to the several thousand-cell stage, the number of ancestral cells is constant: approximately 40 cells are present that will give rise to progeny in the pigmented retina. Analysis of the size of clones in the pigmented retina indicates that the cells of this tissue do not arise through a rigid series of cell divisions originating in the early embryo. The findings that each cleavage stage cell contributes to the pigmented retina and yet the contribution of such cells is highly variable are consistent with the interpretation that clonal descendants of different blastomeres normally intermix extensively prior to formation of the pigmented retina.

Animals↗

PubMed1989

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical course and circulating T cells.

Eight patients with arthritis (seven with rheumatoid, one with psoriatic arthritis) were treated for 7 d with a daily injection of 10 mg of mouse monoclonal anti-CD4 antibodies (three with VIT4, five with MT151). With the exception of a short-lasting low-grade fever in one patient, no side effects were observed. Clinical symptoms (morning stiffness, number of swollen joints, pain assessment and Ritchie articular index) improved in all patients within 7 d of treatment. Improvement lasted from 3 weeks to greater than or equal to 5 months (mean approximately 11 weeks). Rheumatoid factors, immune complexes and other laboratory parameters did not change during or after treatment. Skin reactivity to recall antigens was suppressed in four out of six patients during treatment but returned to pretreatment levels within 6 weeks. Immunofluorescent analysis revealed a short-lasting drop of T cells, mainly of the CD4+ CDw29+ subset, but monocytes were also affected. The injected antibody was detectable on circulating cells for about 10 h. Within 20-24 h, the cell distribution returned to pretreatment levels. In six out of eight patients an anti-mouse-Ig response was seen. We conclude that mouse anti-CD4 monoclonal antibody (MoAb) treatment is well tolerated and that the cellular immunological changes observed are short-lasting. The low incidence of side effects may justify further clinical studies to evaluate the clinical efficacy of such treatment.

Antibodies, Anti-Idiotypic↗

PubMed1989

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: II. Effect of in vivo treatment on in vitro proliferative response of CD4 cells.

In treating rheumatoid arthritis (RA) patients with anti-CD4 antibodies (MT151 10 mg/day, 7 d) we observed diminished skin-test response to recall antigens and reduced proliferative response to antigens and mitogens (in vitro) 2-4 h following the injection. To investigate whether this diminished response is due to functional impairment of CD4+ cells, we analyzed the proliferative response of CD4+ cells to various stimuli, in conditions where the CD4 structure was either cross-linked or not. We found that in vivo anti-CD4-antibody-coated cells could be induced to proliferate if the anti-CD4 antibody was cross-linked with an anti-CD3 antibody [BMA030-F(ab')2] added in vitro and per se non-mitogenic. Also, without cross-linking the cell-bound anti-CD4 antibodies, no impairment of the proliferative capacity of CD4-antibody-coated cells could be detected; double fluorescence analyses of phytohaemagglutinin (PHA)- or CD3-stimulated cells showed that a similar proportion of CD4+ cells proliferated before and after anti-CD4-antibody treatment. The diminished proliferation observed following anti-CD4 treatment correlated to the reduced number of CD3+ and CD4+ cells in culture, which suggests that altered cell distribution might be one factor contributing to the impaired immune response.

Antibodies, Monoclonal↗

PubMed1989

An unusual CT appearance in multiple sclerosis.

Multiple sclerosis, presenting with a picture on C.T. resembling neoplasia is discussed. A differential diagnosis is presented.

Adult↗