What is the future of amalgam?
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Composite Resins↗
Biomedical subjects
S Zimmer
Publications and source records attributed to S Zimmer.
[Pro and contra fissure sealing].
Whereas in Germany fissure sealing has just become a routine treatment in caries prevention, scientists from Sweden and Switzerland proclaim this procedure as economically ineffective. This may result from a low caries prevalence in these countries, which means that only few fissures tend to turn into carious lesions without protection by a fissure sealing. Caries prevalence in Germany is still at a higher level. Thus fissure sealing can be considered cost effective. Besides this, from an ethical viewpoint, the protection and reestablishment of health should never be seen only as an economical issue. That is why fissure sealing is highly recommended as a caries preventive procedure.
Adolescent↗
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↗
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↗
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↗
Mivacurium and prolonged neuromuscular block.
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Adult↗
Comparative analysis of transcription and protein release of the inflammatory cytokines interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) following major burn and mechanical trauma.
The precondition for the systematic modulation of host impairing behavior of hyperactivated monocytes following trauma is to fully understand the mechanistic basis of cellular dysfunction. It was the objective of this study to scrutinize the synthesis patterns and the level of regulation of the functionally related inflammatory cytokines interleukin (IL)-1 beta and IL-8 under stressful conditions. We compared the quantity of cytokine protein release in lipopolysaccharide-stimulated in vitro cultures of peripheral blood mononuclear leukocytes with the signal intensity of the corresponding detectable mRNAs. Fourteen patients with major burn or multiple trauma on consecutive days post-trauma and healthy volunteers were studied. We saw an almost identical pattern of synthesis for both monokines during the time of observation, with a considerable impairment until day 5 post-trauma and recovery thereafter. In contrast to IL-1 beta, a clear concurrence between mRNA signal intensity and the quantity of protein release was found in the majority of patients for IL-8. From these data we conclude that the launching mechanisms for the de novo synthesis for both monokines under stress differ greatly, with IL-8 being clearly regulated on the transcriptional level, whereas the downregulation of IL-1 beta occurs, most likely, on the post-transcriptional level.
Adolescent↗
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↗
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↗
Discrimination of transiently applied mechanical loads: breathing vs. pulling.
Two groups of 24 subjects each attempted to discriminate between large elastic and resistive loads during 50 randomized presentations of each load. Breathers inspired from the loads through a J valve, whereas pullers reciprocally stroked the plunger of a 2-liter syringe connected to the J valve. A range of load durations was obtained in each subject by prematurely unloading approximately one-half of the trials at graded times from their onset. Breathers produced random discrimination scores [50.8 +/- 2.5% (SE) correct] when loaded inspirations were shorter than unloaded inspirations [trials in which both loads induced equal airway pressure (and probably respiratory muscle tension) waveforms] and nonrandom discrimination scores (65.7 +/- 2.8% correct) when loaded inspirations were longer than unloaded inspirations (trials in which both loads induced different waveforms). In contrast, pullers produced nonrandom discrimination scores (62.2 +/- 2.9% correct) when loaded airflow durations were shorter than unloaded inspirations [trials in which both loads induced equal line pressure (and therefore limb muscle tension) waveforms]. Supplemental audio feedback related to instantaneous airflow (an expression of movement) improved load perception in breathers (to 64.2 +/- 3.0% correct; P < 0.01), indicating that airflow feedback introduced load-specific information that was lacking during breathing but redundant during pulling. In support of this hypothesis, airflow feedback by itself enabled a third group of listeners to identify load type with equal accuracy as pullers but with greater accuracy than breathers. These findings suggest that 1) uniformed subjects rely heavily on feedback from airway pressure and/or muscle tension receptors to perceive added loads to breathing and 2) limb mechanoreceptors provide a more sensitive appreciation of movement than do respiratory mechanoreceptors.
Acoustic Stimulation↗
[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↗
Increasing N-CAM-mediated cell-cell adhesion does not reduce invasion of RSV-transformed WC5 rat cerebellar cells.
The WC5 rat cerebellar cell line, infected with a Rous sarcoma virus (RSV) that is temperature-sensitive for pp60v-src transformation, expresses high levels of the neural cell adhesion molecule, N-CAM, when grown at the non-permissive temperature for pp60v-src activity. At the permissive temperature, N-CAM expression is 4- to 10-fold reduced and the cells aggregate poorly. To evaluate the effects of variations in N-CAM expression, we compared the invasive ability of transformed WC5 cells that express low levels of N-CAM with transformed cells in which N-CAM-mediated adhesion was restored. WC5 cells were transfected with expression vectors containing cDNAs encoding the 120 or 180 kDa forms of chicken N-CAM linked to constitutive promoters. Several permanently transfected lines that expressed chicken N-CAM at the cell surface were isolated. These cell lines showed enhanced aggregation at the permissive temperature relative to untransfected WC5 cells or cells transfected with control constructs. By comparing the ability of control and transfected WC5 cells to invade reconstituted extracellular matrix, we tested the effect of variations in N-CAM-mediated adhesion on invasion. Clones that expressed high levels of N-CAM showed invasion rates that were similar to control cells, indicating that increasing N-CAM-mediated adhesion does not inhibit the invasiveness of RSV-transformed WC5 cells.
Animals↗
Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signalling.
The study was performed to further elucidate the mechanisms of dysfunctional T-cell activation following extensive burn and mechanical injuries. The major regulatory level of interleukin-2 (IL-2) release under stressful conditions was determined via parallel analysis of IL-2 messenger RNA (mRNA) expression and IL-2 protein synthesis in mitogen-stimulated peripheral blood mononuclear cell (PBMCs) cultures on consecutive days postinjury. Furthermore, we wanted to scrutinize if inadequate lymphokine production after trauma is possibly a result of defective transduction of extracellular signals to the T-cell nucleus. Fourteen patients (11 men, 3 women, average age 38 +/- 6 years, Injury Severity Score 34 +/- 2) were included in the study. The PBMCs were isolated on days 1, 3, 5, 7, and 10 and stimulated either with the mitogen phytohemagglutinin (PHA) alone or in combination with the protein kinase C (PKC) activator phorbol myristate acetate (PMA). The protein release was examined via bioassay (human con-A blasts) from the supernatants, and the cellular RNA was indicated by radioactive hybridization with the specific complementary DNA (cDNA) after Northern blotting. The IL-2 protein synthesis generated in PHA-stimulated PBMC cultures following trauma, compared with that in controls (0.62 +/- 0.04 U/mL) was persistently and significantly depressed during the observation time with a 57% inhibition on day 10-identical with that on day 1. The Northern blot analysis of IL-2 mRNA expression in the lysates of PHA-stimulated cell cultures after trauma could not detect any mRNA signal for IL-2, in contrast to the control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The influence of major trauma on the regulatory levels of interleukin-1 (IL-1) and IL-2 in human mononuclear leukocytes.
The monokine Interleukin-1 (IL-1) and the lymphokine IL-2 are playing a crucial role within the course of an intact cell mediated immune response (CMI). It was the objective of this study to further elucidate the cytokine associate mechanisms of dysfunctional T-cell activation following major burn and mechanical trauma. Via comparative analysis of mRNA expression and protein release the major regulatory levels of IL-1 and IL-2 release under stressful conditions were to be determined in mitogen respectively LPS stimulated PBMC (peripheral blood mononuclear cells) cultures on consecutive days (D) 1, 3, 5, 7 and 10 post injury. Further, we wanted to scrutinize if inadequate IL-2 production post-trauma is possible due to a defective transduction of extracellular signals to the T-cell nucleus. In order to answer this question IL-2 mRNA expression and IL-2 protein releases were determined in PBMC cultures using the phosphokinase C (PKC) activator phorbol ester (PMA) as a costimulus together with PHA. When analyzing the cumulative data for IL-1 beta we saw until D 5 post-trauma a considerable impairment of the protein release in LPS stimulated PBMC cultures and recovery thereafter. In only a few individual PBMC cultures we saw a concurrence between the IL-1 beta mRNA signal intensity and the protein production. In the majority of the autoradiographies analyzed, the mRNA expression for IL-1 beta was considerably more distinct compared to controls while the corresponding protein release values were on control level or below. These results implicate that the suppression of IL-1 beta post-trauma is regulated mainly on a posttranscriptional level. Since Prostaglandin E2 (PGE2) has been found to have a vigorous impact on the IL-1 beta synthesis on the translational level, we assume that the high PGE2 levels post-trauma inhibit--via cAMP--sufficient IL-1 beta synthesis on the posttranscriptional level. IL-2 protein synthesis as well as mRNA expression in mitogen (PHA) stimulated PBMC cultures following trauma, was persistently and significantly depressed compared to controls during the time of observation. The addition of PMA as a costimulus to PHA, could induce very distinct mRNA signals for IL-2 with a signal intensity which was comparable to that found in the cells of healthy controls. Also the quantity of IL-2 protein release in the vast majority of all patients PBMC cultures following PHA/PMA induction was within the control range.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
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↗
The filing of photographic prints.
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Cataloging↗
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↗