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K Schenck

Publications and source records attributed to K Schenck.

At least 19 recordsLinked to original sources
PubMed2006

Full-mouth tooth extraction lowers systemic inflammatory and thrombotic markers of cardiovascular risk.

Prior studies of a link between periodontal and cardiovascular disease have been limited by being predominantly observational. We used a treatment intervention model to study the relationship between periodontitis and systemic inflammatory and thrombotic cardiovascular indicators of risk. We studied 67 adults with advanced periodontitis requiring full-mouth tooth extraction. Blood samples were obtained: (1) at initial presentation, immediately prior to treatment of presenting symptoms; (2) one to two weeks later, before all teeth were removed; and (3) 12 weeks after full-mouth tooth extraction. After full-mouth tooth extraction, there was a significant decrease in C-reactive protein, plasminogen activator inhibitor-1 and fibrinogen, and white cell and platelet counts. This study shows that elimination of advanced periodontitis by full-mouth tooth extraction reduces systemic inflammatory and thrombotic markers of cardiovascular risk. Analysis of the data supports the hypothesis that treatment of periodontal disease may lower cardiovascular risk, and provides a rationale for further randomized studies.

Adult↗
PubMed2004

Mast cells--a role in periodontal diseases?

OBJECTIVES: Limited attention has been given to the role mast cells may play in periodontal diseases. BACKGROUND: Mast cells are indeed found abundantly below and within several types of mucosal epithelia. On the basis of their proteinase content, mast cells are divided into connective tissue (CT) and mucosal phenotypes. The CT phenotype contains both tryptase and chymase (MC(TC)), while the mucosal phenotype contains only tryptase (MC(T)). The in vivo significance of different mast cell phenotypes has not yet been fully established. Mast cells are able to phagocytose, process and present antigens as effectively as macrophages. RESULTS: Recently mast cells were found in high numbers in chronically inflamed gingival tissue taken from patients with chronic marginal periodontitis (CMP). The number of mast cells was found to be even higher in HIV(+) patients with CMP. Furthermore, mast cells also express strongly matrix metalloproteinases (MMPs), which are key enzymes in degradation of gingival extracellular matrix. Mast cells may release preformed cytokines directing local innate and adaptive immune responses. The present review will focus on possible roles for mast cells in periodontal diseases. CONCLUSIONS: We certainly feel that this is a key cell in inflamed periodontal tissue and its role in periodontitis needs to be revisited.

Cytokines↗
PubMed2003

Matrix metalloproteinases and their inhibitors in gingival mast cells in persons with and without human immunodeficiency virus infection.

BACKGROUND: Mast cells are a prominent cell type in the gingival infiltrate in periodontitis. In this study we examined the expression by gingival mast cells of matrix metalloproteinases, MMP-1, MMP-2, MMP-8 and the tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. METHODS: Gingival specimens from 12 human immunodeficiency virus-negative (HIV-) and 15 HIV-positive (HIV+) patients with chronic marginal periodontitis (CMP), and from 10 HIV- and four HIV+ controls with clinically healthy gingiva (HG) were examined after double immunofluorescence staining for mast cell tryptase, combined with antibodies for MMP-1, MMP-2, MMP-8 or their inhibitors TIMP-1 and TIMP-2. RESULTS: In the HIV+CMP, HIV+HG and HIV-CMP groups, all mast cells expressed MMP-1 and MMP-8, whereas a smaller proportion (40-60%) in the HIV-HG controls displayed such staining. The former groups also displayed a significantly higher proportion (39-64%) of mast cells expressing MMP-2 as compared with the HIV-HG group (21-31%). All groups displayed similar proportions of TIMP-1 expressing mast cells (86-100%), whereas significantly increased proportions of TIMP-2+ mast cells were seen in the HIV+CMP, HIV+HG and HIV-CMP groups (18-25%) as compared with the HIV-HG group (8-13%). Mast cells were the cell type that most prominently expressed MMP-1 and MMP-8. MMP-2 expression was also strong in mast cells, but was also similarly expressed in other cell types. CONCLUSION: The chronically inflamed periodontal lesions in the present study appeared with little evidence of mast cell degranulation. The results show, however, that mast cells in inflamed gingiva have the potential to degrade extracellular matrix if appropriately triggered.

Adult↗
PubMed2003

Liver metastasis of cancer facilitated by chemokine receptor CCR6.

When injected subcutaneously, mouse plasmacytoma (MOPC315) grew rapidly in situ, and metastatic cells became detectable first in the lymph nodes (LNs) and bone marrow, and later in the liver and lungs. We studied MOPC315 cell migration by tracking metastatic cells labelled with green fluorescent protein (GFP). We measured the levels of their chemokine receptor mRNA (by semiquantitative and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), because chemokines can regulate organ predilection of metastasis. Freshly sorted metastatic cells and tumour cell lines derived from the liver of BALB/c mice overexpressed functional CCR6 and CCR7 molecules compared with primary tumour. Preincubation with the CCR6 ligand (CCL20) induced liver-sorted tumour cells to preferentially colonize the liver, demonstrating an association between liver metastasis and CCR6 expression in the mouse. Because the liver is a common site for metastasis, second only to draining LNs, we wished to ascertain whether this finding could be generalized, i.e. whether other cancers can use the similar mechanism of metastasis to the liver, and whether it holds true for humans. We found that CCR6 is overexpressed in small liver metastases of colon, thyroid and ovarian carcinomas compared with normal liver. Because human liver constitutively expresses CCL20, it could attract and select CCR6+ cancer cells. We suggest that chemotaxis via CCR6 might be a common mechanism by which malignant cancers metastasize to the liver. As metastasis in patients with cancer poses the biggest peril for survival, inhibition of CCR6 signalling, either during or after medical or surgical treatment, might be useful in preventing liver metastasis.

Animals↗
PubMed2002

Parotid salivary S-IgA antibodies during experimental gingivitis in smokers and non-smokers.

Persons who smoke display a less pronounced increase of gingival bleeding in the experimental gingivitis model as compared with non-smokers. The aim of the present study was to investigate whether this could partly be explained by differences in levels of parotid total secretory IgA (S-IgA) or parotid S-IgA reactive with selected oral microorganisms. Parotid saliva samples were obtained from 11 smoking and 14 non-smoking volunteers, at baseline, after 5 and 14 days of full mouth experimental gingivitis. Output levels of total S-IgA and of specific S-IgA reactive with cell extracts from Actinobacillus actinomycetemcomitans, Actinomyces naeslundii, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, Peptostreptococcus micros, Streptococcus gordonii and Streptococcus mutans were determined in the samples by means of ELISA. Smokers and non-smokers were found to have similar output levels (microg/min) of total S-IgA, and the values did not significantly change during the experimental gingivitis trial. Parotid salivary outputs (units/min) of the bacteria-specific S-IgA at baseline and at days 5 and 14, were not different between smokers and non-smokers; no changes were observed during the experimental gingivitis trial. The present observations indicate that total S-IgA and bacteria-specific S-IgA in saliva are not main factors that can explain the less pronounced increase of gingival bleeding in the experimental gingivitis model in smokers as compared with non-smokers.

Actinomyces↗
PubMed2001

N-[3-(2-Dimethylaminoethyl)-2-methyl-1H- indol-5-yl]-4-fluorobenzamide: a potent, selective, and orally active 5-HT(1F) receptor agonist potentially useful for migraine therapy.

Recent studies have demonstrated that selective 5-HT(1F) receptor agonists inhibit neurogenic dural inflammation, a model of migraine headache, indicating that these compounds may be effective therapies for the treatment of migraine pain. This communication describes the synthesis and discovery of a novel compound, N-[3-(2-(dimethylamino)ethyl)-2-methyl-1H-indol-5-yl]-4-fluorobenzamide (4), which possesses high binding affinity and selectivity at the 5-HT(1F) receptor relative to more than 40 other serotonergic and nonserotonergic receptors examined.

Animals↗
PubMed2001

Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine.

The interaction of the psychotropic agent olanzapine with serotonin 5-HT(3) and 5-HT(6) receptors was investigated. Olanzapine did not contract the isolated guinea pig ileum, but blocked contractions induced by the 5-HT(3) receptor agonist 2-methyl serotonin (2-CH(3) 5-HT) with a pK(B) value of 6.38+/-0.03, close to the affinity of the 5-HT(3) receptor antagonist ondansetron. The atypical antipsychotic risperidone (1 microM) did not significantly inhibit 2-CH(3) 5-HT-induced contractions. Olanzapine had high affinity (pK(i)=8.30+/-0.06) for human 5-HT(6) receptors in radioligand binding studies. Olanzapine did not stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to the G protein G(s) in cells containing human 5-HT(6) receptors, but inhibited 5-HT-stimulated [35S]GTPgammaS binding (pK(B)=7.38+/-0.16). Among other antipsychotics investigated, clozapine antagonized 5-HT(6) receptors with a pK(B)=7.42+/-0.15, ziprasidone was three-fold less potent, and risperidone, quetiapine and haloperidol were weak antagonists. Thus, olanzapine was not an agonist, but was a potent antagonist at 5-HT(6) receptors and had marked antagonism at 5-HT(3) receptors.

Animals↗
PubMed2001

Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level.

Antigen-presenting cells (APCs) from subcutaneous mouse MOPC315 plasmacytoma phagocytosed immunoglobulin G-coated magnetic beads, enabling efficient isolation within 2 hours by magnetic separation (APC-MB). Cell morphology was heterogeneous, with some of the cells having dendrites. The surface phenotype of purified tumor APCs-MB was CD11b(+), CD11c(+), CD40(+), CD80(+), CD86(+), and MHC class II(+). Tumor APCs-MB expressed messenger RNA for fractalkine and ABCD-1 chemokines, and for CC-type chemokine receptors CCR5 and CCR7, indicating the presence of mature dendritic cells (DCs). Visualized at a single cell level within 4 hours after disruption of the tumor, APCs-MB induced rapid Ca(++) mobilization in MHC class II-restricted tumor idiotype (Id)-specific cloned CD4(+) T cells. In long-term assays, tumor APCs-MB induced proliferation of naive T cells from Id-specific T-cell receptor transgenic mice. The results suggest that tumor APCs-MB represent a heterogeneous cell population that includes myeloid-derived DCs of various stages of maturation. A considerable fraction (> or = 15%) of DCs is spontaneously primed with tumor-specific antigen.

Animals↗
PubMed2000

Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells.

Multiple myelomas produce tumor-specific antigen (TSA) in the form of idiotype (Id) on monoclonal Ig. CD4(+) T cells can recognize Id-peptide on MHC class II molecules and protect against challenges with MOPC315 cells, which are, as common for myelomas, class II-negative. The present study explains these previous results by demonstrating that Id can be transferred from myeloma cells to antigen-presenting cells (APC), which present processed Id-peptide on their class II molecules to Id-specific T cell receptor-transgenic (TCR-TG) CD4(+) T cells. Id-primed tumor APC were heterogeneous, the majority being dendritic cells with class II(+), CD11b(+) CD11c(+) CD40(+) CD80(+) CD86(+) markers. The APC were localized beneath CD31(+) endothelial cells of tumor microvessels, and their frequency declined with tumor progression. The APC could stimulate Id-specific naive TCR-TG, short-term polarized TCR-TG, and cloned CD4(+) T cells to proliferate and produce cytokines in vitro. Furthermore, small MOPC315 tumors established in Id-specific TCR-TG mice contained clusters of activated (CD69(+)CD25(+)) and proliferating (BrdUrd(+)) Id-specific transgenic CD4(+) blasts. The activated Id-specific T cells were located adjacent to Id-primed dendritic cells in the tumor. Thus, a TSA can be transferred in vivo from myeloma, and possibly other types of cancer cells to APC for MHC class II presentation to CD4(+) T cells.

Animals↗
PubMed2000

Fc(alpha) receptor I (CD89) on neutrophils in periodontal lesions.

AIMS: In this study, we have examined the occurrence of FcalphaRI-bearing cells in gingival tissue, gingival fluid and blood, in search for possible roles of IgA and FcalphaRI in periodontal lesions. METHODS: Gingival biopsies from inflamed and healthy sites were obtained from patients with chronic marginal periodontitis. Sections of inflamed gingiva were examined by immunofluorescence techniques and compared to sections from healthy sites. Smears were made from blood and gingival crevicular fluid and similarly studied. RESULTS: Dense infiltrates of neutrophils with strong expression of FcalphaRI (and FcgammaRIII) were found in connective tissue and epithelium of the apical part of periodontal pockets from diseased sites. In contrast, only few such cells were found in healthy gingiva from the same patients. Neutrophils in gingival fluid, tissue and blood expressed FcalphaRI with similar intensity, whereas the expression of FcgammaRIII was significantly decreased in gingival crevicular fluid. Considerable numbers of bacteria from gingival plaque were found to be covered by IgA. CONCLUSION: It is suggested that FcalphaRI on neutrophils may play an important rôle in elimination of IgA-opsonized bacteria, both in periodontal tissue and the adjacent pockets.

Antigens, CD↗
PubMed2000

Reduced numbers of Langerhans cells and increased HLA-DR expression in keratinocytes in the oral gingival epithelium of HIV-infected patients with periodontitis.

BACKGROUND: HIV-seropositive (HIV+) patients become increasingly susceptible to periodontal diseases as HIV infection proceeds. We have previously shown that HIV+ patients with chronic marginal periodontitis (CMP) have remarkably increased numbers of gingival plasma cells in the connective tissue underlying the oral gingival epithelium, but depressed specific serum IgG levels towards periodontopathogenic bacteria. Langerhans cells (LC) and keratinocytes (KC) are antigen-presenting cells that are important in promoting immune responses. METHOD: In this study we examined, by means of immunofluorescence, the distribution and numbers of LC and activated KC in biopsies taken from inflamed periodontal sites in HIV+ and HIV patients with CMP. RESULTS: In the pocket epithelium in both patient groups, basal layer KC expressed HLA-DR molecules. In the oral gingival epithelium of HIV+ patients, basal layer KC also expressed HLA-DR molecules and numbers of LC were decreased as compared with HIV persons. CONCLUSION: The findings suggest that the oral gingiva in HIV+ patients may be affected by inflammation.

Adult↗
PubMed2000

Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT(1F) receptor agonists and PGF(2alpha).

Contractile responses to ergotamine, sumatriptan and the novel 5-HT(1F) receptor agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein. Ergotamine (pEC(50)=8.7+/-0.06) was 30 fold more potent than 5-hydroxytryptamine (5-HT) (pEC(50)=7.2+/-0.13) and 300 fold more potent than sumatriptan (pEC(50)=6.0+/-0.08) in contracting the rabbit saphenous vein in vitro. The selective 5-HT(1F) receptor agonists, LY334370 or LY344864 (up to 10(-4) M), did not contract the rabbit saphenous vein. The contractile response to ergotamine in this tissue resulted from activation of both alpha(1) and 5-HT(1B/1D) receptors based on the observation that prazosin (10(-6) M), an alpha-adrenoceptor antagonist, and GR127935 (10(-8) M) a 5-HT(1B/1D) receptor antagonist, dextrally shifted the contractile response to ergotamine. In contrast, prazosin (10(-6) M) did not alter contraction to sumatriptan whereas GR127935 (10(-8) M) was a potent antagonist (-log K(B)=10.0) suggesting that sumatriptan-induced contraction of the rabbit saphenous vein was mediated only by activation of receptors similar or identical to 5-HT(1B/1D) receptors. PGF(2alpha) (3x10(-7) M) produced a modest increase (approximately 5.0 - 10.0% maximum PGF(2alpha) contraction) in saphenous vein force. Precontraction with PGF(2alpha) (3x10(-7) M) dramatically augmented the potency and maximal contractile response to sumatriptan (pEC(50)=7.1) and modestly enhanced the contractile potency of ergotamine (pEC(50)=9.0) in the rabbit saphenous vein. However, PGF(2alpha) (3x10(-7) M) only unmasked a contraction to the 5-HT(1F) receptor agonists when concentrations exceeded 10(-5) M, concentrations considerably higher than their 5-HT(1F) receptor affinities. LY334370 (10(-6) M) pretreatment did not alter contraction to either sumatriptan or ergotamine and a higher concentration (10(-5) M) of LY334370 or LY344864 inhibited contraction to sumatriptan. Thus, activation of 5-HT(1F) receptors will not induce vascular contraction (either alone or following modest tone with PGF(2alpha)) or augment contraction to other contractile agonists in the rabbit saphenous vein.

Animals↗
PubMed2000

Deletion of idiotype (Id)-specific T cells in multiple myeloma.

Mycloma cells secrete monoclonal immunoglobulin (Ig), called myeloma protein. The variable (V) regions of myeloma proteins are unique to each plasma cell tumor, and therefore contain highly tumor-specific antigenic determinants called idiotopes (Id). T cells with specificity for Id are thought to be of importance in eradication of multiple myeloma. In ongoing clinical trials, myeloma patients are vaccinated against the Id of their own myeloma protein, with the aim of inducing Id-specific T cells. However, this strategy will only succeed if Id-specific T cells are present in patients, and are able to respond. In an experimental animal model, we have shown that [d-specific T cells become progressively deleted as the myeloma protein serum concentration exceeds 50 microg/ml. This indicates that the ability of multiple myeloma patients to respond to Id-vaccination might be seriously handicapped. We suggest that Id-vaccination should be reserved for eradication of minimal residual disease, e.g. after high-dose chemotherapy and stem-cell transplantation.

Animals↗
PubMed1999

Increased levels of soluble Fc gamma receptor III in gingival fluid from periodontal lesions.

Enzyme-linked immunosorbent assay was used for determination of the concentration of soluble Fc gamma receptor III (Fc gamma RIII) in 40 samples of gingival fluid obtained from periodontal pockets in 30 patients with periodontitis. The assay was based on a monoclonal immobilized antibody binding Fc gamma RIII and a polyclonal Fc gamma RIII rabbit antibody for its quantification. The results indicate a substantially increased concentration of soluble Fc gamma RIII in gingival fluid as compared to the serum level. This increased concentration of soluble Fc gamma RIII may interfere with phagocytosis and immune homeostasis in the periodontal lesions.

Animals↗
PubMed1999

The gingival plasma cell infiltrate in HIV-positive patients with periodontitis is disorganized.

Patients infected with the human immunodeficiency virus (HIV) are highly susceptible to chronic marginal periodontitis (CMP) and the lesion is generally characterized by abundant plasma cell infiltration. HIV-induced reduction of CD4+ T cells may indirectly affect local production of immunoglobulins (Ig). Gingival biopsies taken from 10 HIV+ and 12 HIV- control patients with CMP were washed, fixed in ethanol and embedded in paraffin. Sections were examined after immunohistochemical staining with monoclonal antibodies against IgA, IgA1-2, IgG, IgG1-4, IgM and IgE. Ig-containing cells were counted in 3 separate connective tissue zones (subjacent to pocket epithelium, central zone and subjacent to oral epithelium). HIV+ patients showed a remarkably increased density of all Ig-containing cells in the connective tissue zone subjacent to the oral epithelium (p<0.05) and a lower % of IgG2+ cells in the entire gingival section (p<0.05). In HIV+ patients, the density of IgG-containing cells in the gingiva was strongly correlated with the serum IgG concentration. The altered topical distribution might imply impaired restriction of the inflammatory lesion, additional antigenic challenges by unusual microorganisms in the oral cavity, or be secondary to HIV-induced dysregulation of the B-cell system.

Analysis of Variance↗