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S Zimmer

Publications and source records attributed to S Zimmer.

At least 19 recordsLinked to original sources

Ras transformation of cloned rat embryo fibroblasts results in increased rates of protein synthesis and phosphorylation of eukaryotic initiation factor 4E.

Eukaryotic initiation factor 4E (eIF-4E) is a 25-kDa phosphoprotein that binds to the 7-methylguanosine cap of mRNA and acts, along with other eIF-4 polypeptides, to unwind mRNA secondary structure at the 5' terminus. Recent studies have indicated that eIF-4E acts as a protooncogene, but only in its phosphorylated state. In order to determine the role of eIF-4E in oncogenesis, we examined its regulation and expression in cloned rat embryo fibroblasts transformed with the Harvey ras (Ha-ras) oncogene. The expression of Ha-ras increased the rate of protein synthesis but did not increase the levels of eIF-4E mRNA or protein. However, a dramatic increase (7-fold) in phosphate incorporation into eIF-4E was observed. The percentage of eIF-4E in the phosphorylated state was the same in transfected and control cells, indicating that both phosphorylation and dephosphorylation of eIF-4E were increased. Phosphopeptide mapping of eIF-4E from transformed cells indicated a single site of phosphorylation at Ser-53, which is the same as that identified previously in eIF-4E from reticulocytes and HeLa cells. These results indicate that p21ras is part of the signal transduction pathway leading to phosphorylation of eIF-4E. These findings also provide a potential mechanism for cell transformation by p21ras which involves the preferential stimulation of translation of certain mRNAs.

Animals

Invasion by WC5 rat cerebellar cells is independent of RSV-induced changes in growth and adhesion.

The WC5 rat cerebellar cell line, which is infected with a Rous sarcoma virus that is temperature-sensitive for pp60src transformation, shows temperature-dependent expression of the neural-cell-adhesion molecule (N-CAM) and glial fibrillary acidic protein (GFAP). We found that WC5 cells maintained at the non-permissive temperature in both monolayer cultures and spheroids are subject to density-dependent inhibition of growth, whereas cells maintained at the permissive temperature continued to grow. The movement of isolated WC5 cells at both temperatures was similar, while the migration of WC5 cells out of 3-dimensional aggregates was faster at the non-permissive temperature. We tested whether the RSV-induced changes affect the invasion of the WC5 cells in 2 in vitro assays: the chorio-allantoic-membrane assay and the chick-heart-fragment assay. In both assays, WC5 cells grown at either temperature were invasive. These results indicate that growth rate is unrelated to invasion and that loss of N-CAM-mediated cell-cell adhesion is not necessary for invasion.

Animals

In vitro studies of deformation and adhesion properties of transformed cells.

The micropipet aspiration technique and the parallel-plate flow chamber were used to investigate the deformation and detachment properties, respectively, of normal and transformed rat fibroblasts. The normal Cloned Rat Embryo Fibroblasts (CREF) cell line was transfected with the T24 ras oncogene to produce the transformed cell line CREF T24. The CREF T24 cell line was transfected with a Kirsten ras revertant gene (K-rev 1a suppressor) to produce the CT24HKB1 cells, which have the same morphological characteristics as the cells in the CREF line. The cells utilized in this investigation were derived from the parent cell line CREF, the only differences being the presence or absence of the T24 ras oncogene and the Kirsten ras revertant gene. The detachment and deformation properties, therefore, could be related to the metastatic phenotype of the cell rather than inherent differences between disparate cell lines. Results indicated that transfecting the CREF cell line with the ras oncogene greatly modified the detachment and deformation properties. The CREF T24 cells were more easily detached from normal cells and were 50% more deformable. Both CREF and CT24HKB1 showed similar detachment properties. Based on these results, it is speculated that K-rev 1a reversed ras-induced membrane alterations in these cells. Preliminary investigations have demonstrated that both CREF and CREF T24 cells in different phases of the cell cycle differed in morphological characteristics. However, the majority of the cells within a given cell line showed similar deformation characteristics. Current investigations are focusing on characterization of both detachment and deformation properties of these cells as a function of the cell cycle using synchronization techniques.

Animals

The effects of shear stress and metastatic phenotype on the detachment of transformed cells.

A parallel-plate flow chamber was used to quantify the detachment of normal, transformed, and reverted rat fibroblasts from a confluent monolayer of normal fibroblasts. In this method, known shear stresses were applied to the adherent cells and the percent of cells detached from the monolayer was determined. Results indicate that the detachment of all cell types increased with increasing shear stress and detachment of highly metastatic ras-transformed cells was significantly higher than that of either nonmetastatic normal cells or transformed cells reverted with the Kirsten ras revertant (K-rev 1a) gene, which are lowly metastatic. From these results, it is concluded that a correlation exists between the metastatic phenotype of the cell and its ability to detach from normal cells.

Animals

Viscoelastic properties of transformed cells: role in tumor cell progression and metastasis formation.

The micropipette aspiration technique was used to investigate the deformation properties of a panel of nontransformed and transformed rat fibroblasts derived from the same normal cell line. In this method, a step negative pressure is applied to the cell via a micropipette and the aspiration distance into the pipette as a function of time is determined using video techniques. A standard solid viscoelastic model was then used to analyze the viscoelastic properties of the cell. From these results, it is concluded that a direct correlation exists between an increase in deformability and progression of the transformed phenotype from a nontumorigenic cell line into a tumorigenic, metastatic cell line.

Animals

[Cytology of bacterial vaginosis].

Bacterial vaginosis seems to be one of the most frequent cause of vaginal diseases which may be ascending and separates a not aesthetical discharge. A pH greater than 4.5 is found, the presence of clue cells, and a positive sniff test referring to Mobiluncus. The main microorganisms causing bacterial vaginosis are Gardnerella vaginalis and Mobiluncus sp. These are anaerobic ones. Cytology is able to give a quick and sure diagnosis.

Colposcopy

Effects of adenosine on human coronary arterial circulation.

Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine

[Public education in recognizing melanoma].

We report on the first German "melanoma screening week" (Offenbach Melanoma Week). According to the model of the Melanoma/Skin Cancer Detection Week in Dayton/Ohio, the population of Offenbach (100.000 inhabitants) were informed about cutaneous malignant melanoma and its early recognition by means of public media, in particular the local press; the people were asked to participate in a voluntary screening including examination of the entire skin. These examinations were offered in 5 local dermatological practices on 5 working days during the European Week Against Cancer in May, 1988, under the auspices of the Hessian Cancer Society. With 2 to 4 dermatologists daily volunteering, a total of 697 persons were screened. Their average age was 48 years. An illustrated brochure ("Red Light for Black Cancer") with instructions for self-examination of the skin served as a consultation basis and memory aid. The screening week was concluded by a 3-hour's question time ("The citizen asks - the expert answers"). The most surprising result of this campaign was the fact that - contrary to earlier experience - 76% of the persons seeking advice were well aware of "black" cancer. The sole new melanoma detected was an extended lentigo maligna melanoma on the right cheek, which had not been noted during a prophylactic medical examination (!) 2 weeks before. The high public awareness of melanoma and the extremely low percentage of undetected melanomas in Hesse are most probably the result of the 8-year's educational campaign against "black" cancer.

Germany, West

Hypoxic pulmonary vasoconstriction is unaltered by creatine depletion induced by dietary beta-guanidino propionic acid.

It has been suggested that a specific phosphagen pool might serve a sensor function, allowing direct detection of alveolar hypoxia by the pulmonary vascular smooth muscle. The possibility that phosphocreatine (PCr) levels could serve as such a sensor was assessed in isolated rat lungs. Pulmonary vascular reactivity to angiotensin II and alveolar hypoxia was assessed in lungs from control and PCr-depleted rats. PCr depletion was accomplished by feeding rats a diet containing 2% beta-guanidino propionic acid (beta-GPA), an competitive inhibitor of creatine uptake. Total creatine was depleted in beta-GPA lungs, compared to control lungs (p less than 0.05). Lung PCr levels were undetectable by the available 31P NMR spectroscopy system. PCr and creatine were depleted in hearts from beta-GPA rats relative to control hearts (p less than 0.001). Normoxic pulmonary artery pressure and the pressor responses to angiotensin II and hypoxia were not qualitatively or quantitatively altered by the diet indicating either that PCr is not a critical participant in hypoxic pulmonary vasoconstriction or that the degree of PCr depletion achieved was inadequate to expose its role in the hypoxic pressor response.

Animals

Isolation and immunological characterization of a group of new B lymphomas from CBA mice.

We have isolated and characterized a new series of B lymphoma which occurred spontaneously in a group of CBA/N mice that were transferred with spleen or lymph node cells from 24-month-old CBA/Ca mice. Tumor cell lines from six CBA/N mice that received spleen cells were rescued and designated as BKS-2, BKS-3, BKS-4, BKS-5, BKS-6, and BKS-7. Also, tumor cells from a recipient of lymph node cells were rescued and the resulting cell line was designated BKL. These tumor cells expressed membrane immunoglobulin (mu, kappa), major histocompatibility complex Class I and Class II molecules, B220, Lyb8, Fc receptors, J11d, interleukin 2 receptors, and Ly1. All of the tumors did not express the T cell specific markers Thy 1.2, L3T4, and Lyt2.1. They appeared to be clonal in origin, since they exhibited common rearrangements at both heavy and light chain immunoglobulin loci. Phenotypically, these lymphomas appeared to be analogous to immature B cells. Also, these lymphomas displayed different functional reactivities when treated with various B cell mitogens and growth factors in vitro. Anti-mu antibodies which normally induce B cell growth inhibited the proliferation of these lymphoma cells in vitro, whereas they responded to lipopolysaccharide, T cell-derived growth factors, and interleukin 5 by enhanced proliferation. These tumor cells expressed constitutively high levels of c-myc mRNA.

Animals

Cuff herniation.

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Equipment Failure

[Cyto- and histomorphologic changes in the Jensen sarcoma exposed to cisplatin, radiotherapy and combination treatment].

Puncture-cytological and histomorphological investigation results are presented in transplanted tumor Jensen sarcoma. The tested tumors did not respond to therapy in growth reaction and reached a quarter of the body mass of the experimental animals on day 18 post transplantation. Within the five groups (untreated, cisplatin daily 0.6 mg/kg b.w., irradiated with 2 Gy S. D., 20 Gy T. D. only, and 2 groups combined therapy cisplatin and irradiation) cytological differences were shown between the several therapeutic groups already at therapy day 7 in spite of similar growth reaction, but not between centre and periphery of tumors, that were marked more distinctly and confirmed in histomorphological picture at the end of therapy at day 18 p.t. The increased occurrence of giant cells with many nuclei and leukocytic inflammation reaction seem to be a typical picture for combined therapy.

Animals

[Significance of sources of error and quality control in cytologic mass screening].

The cervical mass screening programme in the GDR (since 1973) indicates a high degree of participation exhibiting a sufficient specificity. The sensitivity however has to become better. The main cause of false negative diagnoses is the insufficient gaining materials from the endocerrix channel. This may be corrected by a new plastic spatula. Both the consequent education of the prescreeners and collective final diagnoses may give further help to reduce cytological false negative diagnoses. False positive diagnoses are less fatal. They may be corrected by repeated controls, by special consultations, and by histology.

Cervix Uteri

Induction of the c-myc protooncogene after antigen binding to hapten-specific B cells.

The stimulation of hapten-specific B cell populations with the thymus-dependent antigen, TNP-KLH, was found to induce elevated levels of c-myc mRNA by 2 h. A similar treatment with carrier protein alone did not elevate c-myc mRNA above the level seen in the nonstimulated, resting B cells. These results indicate that antigen binding to the sIg receptor, in the absence of Th cell involvement, directly signals the antigen-binding cell and implicates the active participation of sIg during the process of antigen-mediated B cell activation.

Animals