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Biomedical subjects

S Zimmer

Publications and source records attributed to S Zimmer.

At least 19 recordsLinked to original sources
PubMed1995

Metastasis of C1300 and TBJ murine neuroblastomas correlates with expression of matrix metalloproteinases.

Because metalloproteinases, specifically type IV collagenases, may mediate metastasis, 72- and 92-kDa collagenase activities were evaluated in two murine neuroblastoma cell lines: non-metastatic C1300 and metastatic TBJ. Zymogram analysis demonstrated that 72- and 92-kDa collagenases were associated only with metastatic TBJ. Three human neuroblastoma cell lines were then evaluated by zymogram and Western blot analyses: 72-kDa collagenase was found in metastatic SK-N-SH and IMR-32, but not in SK-N-MC, which may be a peripheral neuroectodermal tumor and not a neuroblastoma. Therefore, 72- and 92-kDa collagenases may be markers of metastasis in neuroblastoma and may aid in differentiation from other small blue cell tumors.

Animals↗
PubMed1995

Detachment of transformed cells. Role of CD44 variants.

A parallel-plate flow chamber was used to quantify the detachment of normal cloned rat embryo fibroblasts (CREF) fibroblasts, ras-transformed CREF fibroblasts (CREF T24), and CREF T24 fibroblasts transfected with a Krev/RAP1A suppressor gene (HK B1) from a confluent monolayer of normal CREF fibroblasts to determine if the expression patterns of CD44 variants (mol wt 110 and 140 kDa) corresponded with detachment properties and metastatic potential. In the detachment assay, known shear stresses ranging from 20-24 dyn/cm2 were applied to the adherent cells and the number of cells detached from the monolayer after 180 s was determined. Results showed that cellular expression of CD44 variants correlated with the metastatic potential of the cells and with the cells' ability to detach from a monolayer of normal cells. Western blot analysis showed a low level of expression of the CD44 variants in the normal cell line, CREF, and the lowly metastatic cell line, HK B1. Detachment studies showed a low percentage of detachment of both of these cell lines from a normal cell monolayer. Tumor-derived (HK B1-T) and lung nodule-derived (HK B1-M) cell lines were established and both formed tumors and metastasis with reduced latency periods as compared to HK B1, but still showed a markedly delayed latency period compared to the highly metastatic cell line, CREF T24. Both of these cell lines showed a higher expression of the CD44 variants as compared to CREF and HK B1, and detached easier than CREF and HK B1. CREF T24 showed a much higher level of expression of the variants and had a higher percentage detachment than all other cell lines. To further test the role of the CD44 variants in the ability of the cells to detach from the normal monolayer, CREF cells were transfected with a DNA construct that constitutively expresses the CD44 variants and the detachment properties of three randomly selected clones were studied. Clones 2 and 3 showed a low level of expression of the CD44 variants after transfection and detached from the normal monolayer similar to CREF. Clone 1 showed a high level of expression of the CD44 variants and the detachment of these cells was significantly higher than CREF. From these results, it is concluded that in the five cell lines studied, expression of the CD44 variants play a significant role in the ability of the cells to detach from a monolayer of normal cells. It is hypothesized that this detachment may be an important component of a cell's ability to metastasize.

Animals↗
PubMed1995

Opposing actions of thrombin and protease nexin-1 on amyloid beta-peptide toxicity and on accumulation of peroxides and calcium in hippocampal neurons.

Amyloid beta-peptide (A beta) is the principal component of neuritic plaques in the brain in Alzheimer's disease (AD). Recent studies revealed that A beta can be neurotoxic by a mechanism involving free radical production and loss of cellular ion homeostasis, thus implicating A beta as a key factor in the pathogenesis of AD. However, other proteins are present in plaques in AD, including the protease thrombin and protease nexin-1 (PN1), a thrombin inhibitor. We therefore tested the hypothesis that thrombin and PN1 modify neuronal vulnerability to A beta toxicity. In dissociated rat hippocampal cell cultures the toxicity of A beta was significantly enhanced by coincubation with thrombin, whereas PN1 protected neurons against A beta toxicity. A beta induced an increase in levels of intracellular peroxides and calcium. Thrombin enhanced, and PN1 attenuated, the accumulation of peroxides and calcium induced by A beta. Taken together, these data demonstrate that thrombin and PN1 have opposing effects on neuronal vulnerability to A beta and suggest that thrombin and PN1 play roles in the pathogenesis of neuronal injury in AD.

Amyloid beta-Peptides↗
PubMed1995

Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury.

Protease nexin-I (PN-1) is a 44 kDa serine proteinase inhibitor that rapidly inhibits thrombin by forming SDS stable complexes with serine at the catalytic site of the protease. Levels of both PN-1 and thrombin are increased in the brain in response to insults such as ischemia, suggesting roles in neural injury and repair processes. We now report that PN-1-protected cultured rat hippocampal neurons against glucose deprivation- induced damage (GDID), and the protection was abolished by equimolar thrombin. PN-1 reduced resting intracellular free calcium levels ([Ca2+]i) and attenuated the elevation of [Ca2+]i normally associated with GDID. Thrombin reduced neuronal survival and caused a significant increase in [Ca2+]i. Submaximally toxic levels of thrombin exacerbated GDID. Calcium responses to thrombin were attenuated in neurons contacting PN-1 immunoreactive astrocytes. These findings suggest that PN-1 and thrombin play important roles in modulating neuronal calcium responses, and vulnerability, to metabolic/excitotoxic insults.

Amyloid beta-Protein Precursor↗
PubMed1994

Dye penetration in root canals filled with AH26 in different consistencies.

It is recommended that the powder to liquid ratio of AH26 be very high and that the mixture be warmed to decrease viscosity before insertion into the root canal. In this study, the effectiveness of the powder to liquid ratio and temperature were assessed using 60 root canals of maxillary central incisors randomly divided into four groups after their cleaning and shaping. The teeth were obturated by either lateral condensation or the single-cone technique using AH26 warmed or at room temperature. After exposure to basic fuchsin, the teeth were embedded and cross-sectioned using a diamond saw. The dye penetration was measured microscopically and reported as a percentage of the total circumference of the filling of each slice using a goniometric eye-piece. After statistical analysis, it was concluded that AH26 in combination with lateral condensation leads to less leakage when used at room temperature.

Bismuth↗
PubMed1994

[Diagnosis of caries risk within the scope of group prevention].

Dental epidemiological research in Germany has recently shown that the major part of caries affected teeth is only found in a small part of the population. This finding mainly refers to children and adolescents. Three quarters of all carious teeth for instance are found in one third of children aged 8 to 9 years. This fact requires intensified preventive proceedings for children with an apparently increased caries risk. Caries preventive steps, however, can only be effective if the identification of children with increased risk takes place before the first carious damage has occurred. Actually, there is no method to solve this problem in an optimal way. Under this restriction the Dentoprog-method which has been developed at the University of Zurich is considered the best solution for school--based steps in caries prevention.

Adolescent↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1990

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↗
PubMed1989

[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↗
PubMed1989

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↗
PubMed1989

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↗