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Biomedical subjects

S Zimmer

Publications and source records attributed to S Zimmer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical study of the effectiveness of two sonic toothbrushes.

The aim of this study was to determine the oral hygiene effects of two sonic toothbrushes, the Water Pik Sonic Speed (W) and Sonicare (S), compared to a manual toothbrush (Elmex Super 39, E). Thirty-six healthy volunteers between 13 and 69 years of age participated in this single-blind, crossover study. They were randomly assigned to three groups, with 12 participants each. Two weeks after a screening examination, a baseline examination was performed for each participant followed by professional tooth cleaning. Three indices were recorded to assess the oral hygiene status: a papillary bleeding index (PBI), a plaque index for smooth surfaces (PI) and a plaque index for approximal surfaces (API). After instructions on how to use the toothbrushes, each group started the experiment with a different type of toothbrush. After two weeks of application, the indices were recorded a second time. This was followed by two weeks of recess, where each participant used the same brand of manual toothbrush, and then before each group switched to the next toothbrush, participants had another baseline examination and professional tooth cleaning. The three types of brushes were used in the following order: S, E, W; recess; E, W, S; recess; W, S, E. The duration of the study was 12 weeks. A single investigator performed all examinations. The Friedman test and Wilcoxon signed rank test were used for statistical analysis. Compared to the manual toothbrush the Sonic Speed and the Sonicare were more effective in removing plaque and preventing gingivitis. The study indicated that the two sonic toothbrushes may be effective alternatives to a commonly used manual toothbrush.

Adolescent↗
PubMed1999

Phenotype of a recombinant store-operated channel: highly selective permeation of Ca2+.

1. Genes related to trp (transient receptor potential) are proposed to encode store-operated channels. We examined the ionic permeation of recombinant channels formed by stable and transient expression of the TRP homologue bCCE1 in Chinese hamster ovary (CHO) cells (CHO(CCE1)) and rat basophilic leukaemia (RBL) cells, respectively. 2. Store-operated currents were activated in CHO(CCE1) cells by internal dialysis of IP3 under strong buffering of intracellular Ca2+. The action of IP3 was mimicked by thapsigargin but not by IP4. 3. With extracellular Ca2+, Na+ and Mg2+, the store-operated currents of CHO(CCE1) rectified inwardly in the presence of internal Cs+. Outward currents were not detected below +80 mV. Identical currents were recorded with external Ba2+ and also with no external Na+ and Mg2+. In the absence of external Mg2+, the inward currents showed an anomalous mole fraction behaviour between Ca2+ and Na+. Half-maximal inhibition of Na+ currents was observed with approximately 100 nM and full block with 2-5 microM external Ca2+. 4. In the parental CHO(-) cells, IP3 dialysis evoked inward currents that also displayed anomalous mole fraction behaviour between Ca2+ and Na+. However, half-maximal block of Na+ currents required 5 times higher Ca2+ concentrations in CHO(-) cells. Additionally, the density of Ca2+ and Na+ currents at -80 mV was 5 and 2 times larger in CHO(CCE1) cells, respectively. 5. In RBL cells, dialysis of IP3 evoked store-operated currents that showed 1.4-fold larger densities at -80 mV in cells expressing bCCE1. 6. The enhanced density of store-operated currents in CHO(CCE1) cells and in bCCE1-transfected RBL cells probably reflects the phenotype of CCE1. These results suggest a highly selective permeation of Ca2+ through recombinant channels formed by CCE1 either alone or in combination with endogenous channel proteins.

Animals↗
PubMed1999

Ca2+-dependent interaction of the trpl cation channel and calmodulin.

The transient receptor potential-like ion channel from Drosophila melanogaster was originally identified as a calmodulin binding protein (Philips et al., 1992) involved in the dipterian phototransduction process. We used a series of fusion proteins and an epitope expression library of transient receptor potential-like fusion proteins to characterize calmodulin binding regions in the transient receptor potential-like channel through the use of [125I]calmodulin and biotinylated calmodulin and identified two distinct sites at the C-terminus of the transient receptor potential-like ion channel. Calmodulin binding site 1, predicted from searching of the primary structure for amphiphilic helices (Philips et al., 1992), covers a 16 amino acid sequence (S710-I725) and could only be detected through biotinylated calmodulin. Calmodulin binding site 2 comprises at least 13 amino acids (K859ETAKERFQRVAR871) and binds both [125I]calmodulin and biotinylated calmodulin. Both sites (i) bind calmodulin at least in a one to one stoichiometry, (ii) differ in their affinity for calmodulin revealing apparent Ki values of 12.3 nM (calmodulin binding site 1) and 1.7 nM (calmodulin binding site 2), respectively, (iii) bind calmodulin only in the presence of Ca2+ with 50% of site 1 and site 2, respectively, occupied by calmodulin in the presence of 0.1 microM (calmodulin binding site 1) and 3.3 microM Ca2+ (calmodulin binding site 2) and give evidence that (iv) a Ca2+-calmodulin-dependent mechanism contributes to transient receptor potential-like cation channel modulation when expressed in CHO cells.

Amino Acid Sequence↗
PubMed1999

Clinical study on the plaque-removing ability of a new triple-headed toothbrush.

The aim of this study was to determine the plaque removing ability of a new toothbrush with a u-shaped head (Superbrush) compared to a conventional manual toothbrush (Elmex) and an electric toothbrush with a rotating head (Braun Plak control). 36 healthy volunteers, aged 6-60 years, participated in this single blind cross-over study. They were randomly assigned to 3 groups (A, B, C) with 12 participants each. To obtain a plaque-free condition at the baseline, professional toothcleaning was performed in each participant. After instructions on how to use the toothbrushes, each group started the experiment with a different type of toothbrush. After 1 week of application, the Quigley-Hein plaque index (QHI) and the proximal plaque index (API) were used to assess the oral hygiene status of each participant. This was followed by 1 week of recess before each group switched to the next type of toothbrush. The duration of the study was 5 weeks. All examinations were performed by 1 examiner. Compared to the 2 other brushes, the Superbrush was more effective in removing plaque (medians of QHI: 0.84 versus 1.56 (Elmex) and 1.56 (Braun); p<0.001; medians of API: 0.69 versus 0.94 (Elmex) and 0.87 (Braun); p<0.001). The study indicated that the new toothbrush may be an effective alternative to commonly used toothbrushes.

Adolescent↗
PubMed1999

Mediastinal lymph node infiltration in non-small cell lung cancer and its role in curative surgery.

Despite the importance of lymph node infiltration for the classification and prognosis of non-small cell lung cancer (NSCLC), there are no accepted standards for quality of mediastinal lymphadenectomy. In 270 consecutive patients undergoing potentially curative surgery for NSCLC, including complete ipsilateral lymph node dissection, we investigated the possibility of a correlation between tumour location and lymph node infiltration. The tumours were classified as UICC stage I (n = 115), II (n = 42) or IIIa (n = 113). Patients with N2-disease (n = 68) showed up to 81% skip metastasis. Because of the observed dissemination of lymph node metastasis, tumour location could not predict nodal infiltration. The variability of nodal involvement and the frequent occurrence of skip metastasis thus make complete ipsilateral lymphadenectomy mandatory for curative management of NSCLC.

Adenocarcinoma↗
PubMed1999

Identification of a novel cytosolic tocopherol-binding protein: structure, specificity, and tissue distribution.

Alpha-tocopherol plays an important role as a lipid-soluble antioxidant. It is present in all major mammalian cell types and shows tissue-specific distribution. This suggests the presence of specific proteins involved in intracellular distribution or metabolism of alpha-tocopherol. A diminution of tocopherol plasma concentrations contributes to the development of diseases such as vitamin E deficiency (AVED), atherosclerosis, and prostate cancer. Further evidence has been obtained for the existence of sites in cellular metabolism and signal transduction where alpha-tocopherol potentially plays a regulatory role. A signal transduction modulation specific for alpha-tocopherol has been described in several model systems. Using radioactively labeled alpha-tocopherol as tracer, we have isolated a new alpha-tocopherol-associated protein (TAP) from bovine liver. This protein has a molecular mass of 46 kDa and an isoelectric point of 8.1. From its partial amino acid sequence, a human gene has been identified with high homology to the newly described protein. Sequence analysis has established that the new TAP has structural motifs suggesting its belonging to a family of hydrophobic ligand-binding proteins (RALBP, CRALBP, alpha-TTP, SEC 14, PTN 9, RSEC 45). Human TAP has been cloned into Escherichia coli, and its tissue-specific expression has been assessed by Northern blot analysis.

Amino Acid Sequence↗
PubMed1999

Evaluation of Fc-receptor positive (FcR+) and negative (FcR-) monocyte subsets in sepsis.

The monocyte/macrophage (Mphi is central in the regulation of the immune response in states of trauma and sepsis. Because monocyte subsets, characterized by expression of the Fc-receptor (FcR), were shown to play distinct immunologic roles in trauma, it was the objective of this study to assess insights into the functional role of FcR positive (FcR+) and negative (FcR-) subclasses in surgical sepsis. In a prospective study, peripheral blood Mphi from 20 septic patients and 10 healthy volunteers were evaluated on consecutive days after the onset of sepsis. FcR+/- subsets were separated by rosetting with antibody-coated human erythrocytes. Receptor expression and synthesis of proinflammatory cytokines were used to evaluate the functional role of these cells. We demonstrated a significant monocytosis (350%; p<.01) and suppression of human lymphocyte antigen (HLA-DR) expression (35%; p<.05). Synthesis of Interleukin-1beta (IL-1beta; e.g., Day 1: 230+/-30 pg/mL) and Interleukin-6 (IL-6; e.g., Day 1: 1920+/-350 U/mL) were significantly higher (p<.05) in FcR+ subsets than in controls (IL-1beta: 100+/-5 pg/mL; IL-6: 353+/-75 U/mL). Tumor necrosis factor-alpha (TNF-alpha) was elevated in FcR+ monocytes but did not reach a significant value. Interleukin-8 (IL-8) synthesis showed only on Day 1 and in controls significant differences in FcR+ and FcR- cells (Day1: FcR-: 19.6+/-4.1 nM; FcR+: 9+/-4.3 nM). Sepsis results in a significant shift toward FcR+ monocytes. This cell population is characterized by high proinflammatory cytokine synthesis. The extent of this shift seems to identify a group of high risk septic patients that might benefit from immunomodulatory therapy.

Adult↗
PubMed1999

Caries prevention with fluoride varnish in a socially deprived community.

UNLABELLED: It has been suggested that specific preventive programs be developed for children with high caries risk. One possibility is to consider whole classes in socially deprived schools as caries-risk groups and perform an intensified preventive program for the entire class. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of such a program which includes the application of a fluoride varnish (Duraphat). METHODS: The application of the varnish was offered three to four times a year in a community with low socio-economic status and a generally high caries level. Two hundred and sixty-nine children in six primary schools of Linden/Limmer, a district in Hannover, Germany, were allocated to a test or a control group. The test group received the fluoride varnish for 4 years whereas the control group received no professional fluoride application. DMFT was recorded at the beginning of the study and after 4 years. RESULTS: At the end of the study, children who had received a minimum of two fluoride applications per year showed a significantly lower caries increment in comparison with the control group (0.88 DMFT vs 1.39 DMFT, P < 0.05). CONCLUSIONS: It can be concluded that a minimum of two applications of the fluoride varnish Duraphat per year may be an effective measure in preventing caries in socially deprived children with high caries activity.

Child↗
PubMed1999

Adhesion of nonmetastatic and highly metastatic breast cancer cells to endothelial cells exposed to shear stress.

The mechanical stimulus of shear stress has to date been neglected when studying the adhesion of cancer cells to the endothelium. Confluent monolayers of endothelial cells were subjected to either 4 or 15 hours of arterial shear stress. Adhesion of nonmetastatic (MCF-7) and highly metastatic (MDA-MB-435) human breast cancer cells was then quantified using a detachment assay carried out inside the parallel plate flow chamber. Four hours of shear stress exposure had no effect on adhesion. However, 15 hours of shear stress exposure led to marked changes in the ability of the endothelial monolayer to bind human breast cancer cells. An increase in adhesive strength was observed for nonmetastatic MCF-7 cells, while a decrease in adhesive strength was observed for highly metastatic MDA-MB-435 cells. Hence, endothelial shear stress stimulation does influence the adhesion of cancer cells to the endothelium and can have different effects on the adhesion of cancer cells with different metastatic potentials. Furthermore, adhesion of nonmetastatic and highly metastatic human breast cancer cells may be controlled by two different endothelial cell adhesion molecules that are differentially regulated by shear stress. Immunohistochemistry confirmed that shear stress did in fact differentially regulate endothelial cell adhesion molecule expression.

Analysis of Variance↗
PubMed1998

TBJ murine neuroblastoma resists dibutyryl cyclic AMP-induced differentiation and effects on metalloproteinase secretion.

BACKGROUND: Nonmetastatic C1300 murine neuroblastoma and TBJ, a metastatic variant, exhibit different mechanisms of metastasis and invasion. METHODS: In this study, they were examined for response to 1 mmol/L dibutyryl cyclic AMP in vitro. RESULTS: (1) dCAMP induced morphological differentiation in 20% to 40% of C1300 cells, whereas TBJ resisted differentiation. (2) Untreated TBJ expressed 92-kDa metalloproteinase, whereas C1300 expressed none. These results were not affected by dCAMP. (3) Growth curves of untreated C1300 and TBJ were exponential. Dibutyryl CAMP induced a plateau in C1300 growth that was confirmed by increased S-phase cells by cell cycle analysis. CONCLUSIONS: TBJ growth was unaffected by dCAMP. Apoptosis, as assayed by Hoechst-merocyanine staining test, was not involved in the growth plateau.

Animals↗
PubMed1998

Functional analysis of monocyte subsets in surgical sepsis.

BACKGROUND: Sepsis still remains a major cause of death after surgery. Impaired monocyte (Mphi) function and disruption of monocyte (Mphi/T-cell interaction were shown to be crucial for the development of septic complications in these patients. It was the objective of the study to assess more insights in Mphi behavior in surgical sepsis by means of analysis of Fc receptor- and human leukocyte antigen DR (HLA-DR) expression in Mphi subsets, and to evaluate the kinetics of these changes. METHODS: In a prospective study, 20 septic patients and 10 healthy control subjects were included. Peripheral Mphi were isolated on consecutive days after onset of sepsis, and FcR positive (FcR+) and negative (FcR-) subsets were separated by rosetting with antibody-coated human erythrocytes. Cell surface receptor expression and in vitro cytokine production were used to determine the clinical importance of these subsets. RESULTS: A significant monocytosis (3.5-fold; p < 0.01) and suppression of HLA-DR receptor expression (35%, p < 0.01) which correlate with sepsis severity and outcome could be demonstrated. There was a significant increase of FcR+ subsets in sepsis compared with control subjects (60% vs. 24%; p < 0.05). In vitro stimulation of Mphi subsets and peripheral blood mononuclear cells revealed suppressed interferon-gamma synthesis (p < 0.05 up to 0.01) from day 1 to day 5, elevated neopterin release (p < 0.05) on day 14 and increased synthesis rates of proinflammatory cytokines (e.g., interleukin-1beta); p < 0.05) predominantly in FcR+ subsets. CONCLUSIONS: Sepsis results in a significant monocytosis and suppression of HLA-DR receptor expression, which are correlating with sepsis severity and outcome. A significant shift toward FcR+ Mphi subsets can be found. This subpopulation resembles the previously described "angry macrophage" that is characterized by high proinflammatory cytokine synthesis and suppressed antigen presentation and that contributes to a disruption of adequate Mphi/T-cell interaction, rendering the host anergic toward opportunistic infections. The extend of HLA-DR suppression and the shift toward FcR+ Mphi might characterize a high risk patient subpopulation, which could benefit from immunomodulatory strategies.

Adolescent↗
PubMed1998

[Inflammatory syndrome after endovascular implantation of an aortic stent--a comparative study].

Immunological changes as described in endovascular aortic aneurysm repair are not yet fully understood. In several studies this reaction (leukocytosis, fever, high CRP levels) is named as a "postimplantation syndrome". In our study we could show that in the first week after endovascular aortic aneurysm surgery complex immunological changes occur. But these changes do not quantitatively differ from those seen in open aortic aneurysm surgery. Fever (38 degrees C) was apparent in almost all patients. White blood cell count rose up to 10.6 (+/- 0.84) G/L during the first days. CRP, one of the acute phase proteins, was elevated with the maximum on postoperative day 2. Only the open operated patients had elevated alpha 1-antitrypsin levels from the second postoperative day on. IL-6 synthesis was increased in both groups, with an elevation in group B until day 8. The coagulation system was impaired, but was most evident in the open aortic aneurysm group. In this study we could show that both operative techniques had comparable immunological changes. During open aneurysm repair the large operative trauma seems to play a central role, whereas endothel activation might be crucial in endovascular operated patients.

Aged↗
PubMed1997

Alternatively spliced IS6 segments of the alpha 1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and vascular smooth muscle L-type Ca2+ channels.

Dihydropyridines (DHPs) block the vascular smooth muscle L-type Ca2+ channel at lower concentrations than the cardiac Ca2+ channel, although their alpha 1 subunit, which binds the DHPs, is derived from the same gene. This alpha 1C gene gives rise to several splice variants, among which the alpha 1C-b variant is affected by lower concentrations of nisoldipine than the alpha 1C-a variant. Functional expression of chimeras of alpha 1C-a and alpha 1C-b subunits demonstrated that the transmembrane segment IS6 is responsible for the different dihydropyridine sensitivity. Northern blot analysis showed that transcripts coding for the IS6 segment of the alpha 1C-a subunit were expressed in heart but not in aorta, whereas the IS6 segment of the alpha 1C-b subunit was expressed predominantly in vascular smooth muscle. In situ hybridization of rat heart sections confirmed this expression pattern of IS6 alpha 1C-a and IS6 alpha 1C-b in ventricular and smooth muscle myocytes, respectively. These results suggest that the different dihydropyridine sensitivities of cardiac and vascular L-type Ca2+ channels are caused at least partially by the tissue-specific expression of alternatively spliced IS6 segments of the alpha 1C gene.

Alternative Splicing↗
PubMed1996

A mammalian capacitative calcium entry channel homologous to Drosophila TRP and TRPL.

Intracellular Ca2+ signalling evoked by Ca2+ mobilizing agonists, like angiotensin II in the adrenal gland, involves the activation of inositol(1,4,5)trisphosphate(InsP3)-mediated Ca2+ release from internal stores followed by activation of a Ca2+ influx termed capacitative calcium entry. Here we report the amino acid sequence of a functional capacitative Ca2+ entry (CCE) channel that supports inward Ca2+ currents in the range of the cell resting potential. The expressed CCE channel opens upon depletion of Ca2+ stores by InsP3 or thapsigargin, suggesting that the newly identified channel supports the CCE coupled to InsP3 signalling.

Amino Acid Sequence↗
PubMed1996

Update on the mechanisms of immune suppression of injury and immune modulation.

Major trauma results in massive impairment of immunologic reactivity, the clinical consequence of which consists in the high susceptibility of the traumatized individual toward serious infection. Whereas parts of the immune system are stimulated within a systemic, nondiscriminant, excessive whole-body inflammation, other functions within the complex of cell-mediated immunity (CMI) are dramatically paralyzed. Immune abnormalities in the aftermath of trauma occur in a sequence of states of cellular activation and within a complex order of events that is not yet well understood. Traumatic stress is causing disintegration of the intact monocyte (Mphi)-T cell interaction, which is associated with profound changes in Mphi forward-regulatory capacities and substantial depression of T cell function. Extensive tissue destruction results in the generation of numerous stimuli, such as phagocytosis, immune complexes, complement split products, and endo- and exotoxins, all of which contribute to excessive Mphi activation. Mphi then rapidly produce and release prostaglandin E2 (PGE2), a powerful endogenous immune suppressant. PGE2 is an inhibitor of T cell mitogenesis, interleukin 2 (IL-2) production, and IL-2 receptor expression; and it has a massive impact on the quality of B cell antibody synthesis. Most importantly, PGE2 represents an important cofactor for the induction of T-helper lymphocyte (TH) activity toward the TH2 direction. TH2 cells are associated with the synthesis of immunosuppressive cytokines, such as IL-4 and IL-10. Although immunosuppressive substrates are inhibitory for TH1 cells-the functional carriers of CMI-they support TH2 activity, which predisposes the host to develop infection. The endogenous ability of the organism to survive overwhelming trauma is insufficient and requires major exogenous support. Immune modulatory interventions, depending on the immune abnormalities seen in the traumatized host, should be started as early as possible after trauma in a preventive fashion to protect against organ tissue destruction. Ideally, it should protect all cellular host defense compartments from hyperactivation as well as from exhaustion. We do believe that only a combination of drugs can effectively control the posttraumatic dyshomeostasis of the various cell systems.

Adjuvants, Immunologic↗
PubMed1996

Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice.

Intranasal or intramuscular (i.m.) immunization of mice and i.m. immunization of rabbits with formalinized staphylococcal enterotoxin B (SEB) toxoid in saline elicited higher anti-SEB serum immunoglobulin G (IgG) titers when the toxoid was formulated with proteosomes. In addition, intranasal immunization of mice with this proteosome-toxoid vaccine elicited high levels of anti-SEB IgA in lung and intestinal secretions, whereas the toxoid without proteosomes did not. Two i.m. immunizations with proteosome-toxoid plus alum also induced higher murine serum responses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with either saline or alum afforded significant protection against lethal SEB challenge in two D-galactosamine-sensitized murine models of SEB intoxication, i.e., the previously described i.m. challenge model and a new respiratory challenge model of mucosal SEB exposure. Efficacy correlated with the induction of high serum levels of anti-SEB IgG. In contrast, intranasal or i.m. immunization with toxoid in saline without proteosomes was not significantly protective in either challenge model. Proteosome-toxoid plus alum given i.m. also elicited more significant protection against respiratory challenge than the alum-adjuvanted toxoid alone. The capacity of proteosomes to enhance both i.m. and intranasal immunogenicity and efficacy of SEB toxoid indicates that testing such proteosome-SEB toxoid vaccines in the nonhuman primate aerosol challenge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mucosal vaccine delivery system to protein toxoids and suggest that respiratory delivery of proteosome vaccines may be practical for enhancement of both mucosal and systemic immunity against toxic or infectious diseases.

Adjuvants, Immunologic↗
PubMed1996

Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and burns.

OBJECTIVE: To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma. DESIGN: Retrospective study. SETTING: Teaching hospitals, USA and Germany. SUBJECTS: Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points. INTERVENTIONS: Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10). MAIN OUTCOME MEASURES: Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns. RESULTS: High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma. CONCLUSION: Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.

Adolescent↗