Biomedical subjects

K Schenck

Publications and source records attributed to K Schenck.

At least 37 records · Page 2Linked to original sources

PubMed1999

Extensive expression of TGF-beta1 in chronically-inflamed periodontal tissue.

The host immune response in chronic marginal periodontitis (CMP) raised against bacteria colonizing the dentogingival area is modulated by cytokines. This study examines the distribution of the transforming growth factor-beta1 containing (TGF-beta1+) cells in formalin-fixed and paraffin-embedded gingival specimens from 11 patients with chronic marginal periodontitis and 7 persons with healthy gingiva. Inflamed periodontal tissue contained a 100-fold more TGF-beta1+ cells than healthy gingiva. Diverse morphological TGF-beta1+ cell types were discerned. Double immuno-enzymatic and -fluorescence staining revealed that TGF-beta1+ cells comprised 21-29% macrophages 2-3% T-cells, 3-9% B-cells, 34-35% neutrophilic granulocytes and 7-10% mast cells. The densities of all TGF-beta1+ cell types in CMP were strongly increased in the connective tissue adjacent to the pocket epithelium, in the lamina propria and adjacent to the oral epithelium. In lesions with extensive inflammation, expression was also marked in pocket epithelium. TGF-beta1 is an immunosuppressive cytokine that stimulates wound healing. Upregulation of the cytokine in inflamed gingiva may counterbalance for destructive gingival inflammatory responses that are simultaneously taking place in patients with CMP.

Case-Control Studies↗

PubMed1999

Topical distribution of Fc gammaRI, Fc gammaRII and Fc gammaRIII in inflamed human gingiva.

The topical distribution of Fc gamma receptor types I, II and III (Fc gammaRI-III) was analyzed by means of immunohistochemistry in human gingival tissue obtained from 12 patients with chronic periodontitis. CD68+ macrophages expressing all three classes of Fc gammaR were found throughout the whole gingival connective tissue (CT), whereas dense infiltrates of polymorphonuclear granulocytes (identified by staining for neutrophil elastase) with strong staining for Fc gammaRIII and Fc gammaRII were found subjacent to the apical part of the pocket epithelium (PE) and in the PE itself. CD19+ B lymphocytes with variable staining intensity for Fc gammaRII were observed in clusters subjacent to the PE and extending into the central part of the CT. Only a few scattered CD3+ T lymphocytes stained for Fc gammaRIII. Some spindle-shaped cells (CD68-, therefore non-macrophages) and apparently non-cellular fibrous tissue elements stained for Fc gammaRI and Fc gammaRII. In the epithelium, Fc gammaRII+ dendritic cells were frequently observed in the entire oral gingival epithelium and in the coronal part of the PE. Occasionally, some keratinocytes which stained for Fc gammaRII and Fc gammaRIII were found. The observations indicate that Fc gammaR of the various classes are amply expressed on numerous cell types in inflamed gingival tissue. The specific distribution pattern detected suggests that Fc gammaRs may play a role in the mediation of chronic inflammation in the periodontal lesion.

Adult↗

PubMed1999

5-Hydroxytryptamine(1F) receptors do not participate in vasoconstriction: lack of vasoconstriction to LY344864, a selective serotonin(1F) receptor agonist in rabbit saphenous vein.

Recently, several novel approaches to the treatment of migraine have been advanced, including selective 5-hydroxytryptamine (or serotonin) 1B/1D (5-HT(1B/1D)) receptor agonists such as sumatriptan and 5-HT(1F) receptor agonists such as LY344864. Many 5-HT(1B/1D) receptor agonists have been identified based on their ability to produce cerebral vascular contraction, whereas LY344864 was identified as an inhibitor of trigeminal nerve-mediated dural extravasation. In our study, several triptan derivatives were compared with LY344864 for their ability to contract the rabbit saphenous vein, a tissue used in the preclinical identification of sumatriptan-related agonists. Sumatriptan, zolmitriptan, rizatriptan, and naratriptan all contracted the rabbit saphenous vein from baseline tone, whereas LY344864 in concentrations up to 10(-4) M did not contract the rabbit saphenous vein. Furthermore, vascular contractions to sumatriptan were markedly augmented in the presence of prostaglandin F(2alpha) (PGF(2alpha)). However, even in the presence of PGF(2alpha) (3 x 10(-7) M), LY344864 did not contract the rabbit saphenous vein in concentrations well in excess of its 5-HT(1F) receptor affinity (pK(i) = 8.2). Only when concentrations exceeded those likely to activate 5-HT(1B) and 5-HT(1D) receptors (>10(-5) M) did modest contractile responses occur in the presence of PGF(2alpha). Use of these serotonergic agonists revealed a significant correlation between the contractile potency in the rabbit saphenous vein and the affinities of these agonists at 5-HT(1B) and 5-HT(1D) receptors, although contractile agonist potencies were not quantitatively similar to 5-HT(1B) or 5-HT(1D) receptor affinities. In contrast, no significant correlation existed between the contractile potencies of these serotonergic agonists in the rabbit saphenous vein and their affinity at 5-HT(1F) receptors. These data support the contention that activation of 5-HT(1F) receptors will not result in vascular contractile effects.

Animals↗

PubMed1998

Clonal deletion of thymocytes as a tumor escape mechanism.

Clonal deletion of thymocytes is a major event in T-cell tolerance and might represent a tumor escape mechanism. Previously, we have shown that class II-restricted, Id-specific, CD4+ T cells in T-cell receptor (TCR)-transgenic mice confer resistance against the MOPC315 plasmacytoma. In this report, we have investigated whether monoclonal immunoglobulin (Ig) produced by a plasmacytoma can induce deletion of thymocytes specific for the variable parts of Ig, i.e., the idiotype (Id). Large numbers of MOPC315 tumor cells were injected s.c. in the TCR-transgenic mice to overwhelm the CD4+ T-cell-mediated protection. When the MOPC315 plasmacytomas reached a weight of approximately 0.5 g (serum myeloma protein M315 about 50 microg/ml), immature CD4+ 8+ and mature CD4+ transgenic thymocytes became progressively deleted. Apoptotic thymocytes were already detectable when tumors were 2 mm in diameter (serum M315: 5 microg/ml, or 0.03 microM). The negative selection was Id-specific, because an Id-negative plasmacytoma failed to induce deletion. Injection of purified MOPC315-myeloma protein (M315) i.p. caused a profound reduction of Id-specific thymocytes. Enriched thymic dendritic cells (DC) from tumor-bearing animals were found to be primed with lambda2(315) and induced apoptosis of thymocytes in vitro. Our results indicate that circulating myeloma protein is processed and presented by thymic antigen-presenting cells (APC), and induces deletion of Id-specific thymocytes. Deletion of tumor-specific thymocytes may represent a tumor escape mechanism in patients with cancers that secrete or shed tumor antigens. The possibility that vaccination with tumor Ig or genes encoding for it may induce tolerance instead of protection should be taken into consideration.

Animals↗

PubMed1998

Transient overexpression of CD4 enhances allelic exclusion of T-cell receptor (TCR) alpha chains and promotes positive selection of class II-restricted TCR-transgenic thymocytes.

CD4 contributes to antigen recognition of T cells by binding to class II MHC molecules. There is heterogeneity in expression of CD4 coreceptor among CD4+CD8+ thymocytes. We have investigated whether the expression level of coreceptor influences positive selection. Thymocytes of mice expressing transgenic lambda2(315)-Ig-light-chain/I-Ed specific TCR are poorly positively selected because they fail to allelically exclude endogenous TCR alpha chain genes and because there is no skewing towards CD4. Transient overexpression of CD4 during thymocyte development, in mice transgenic for both TCR and CD4, resulted in skewing towards CD4 in the periphery, reduced rearrangement and expression of endogenous alpha-chains, and decreased levels of thymocyte RAG-1 transcripts. Kinetic BrdU labeling experiments showed that single CD4+ thymocytes developed faster, representing the predominant population even in the cortex of the double transgenic thymi. These results demonstrate that increased coreceptor expression can compensate for poorly selectable TCR, supporting avidity and instructional models for positive selection of thymocytes.

Animals↗

PubMed1998

The gingival plasma cell infiltrate in renal transplant patients on an immunosuppressive regimen.

Treatment with immunosuppressive agents inhibits gingival inflammation and progression of periodontitis in humans. We examined the numbers and the isotype distribution of immunoglobulin-producing plasma cells by immunohistochemistry in gingival specimens taken from renal transplant transplant recipients receiving immunosuppressive agents (IS), and from otherwise comparable systemically healthy patients. The immunosuppressed patient group had significantly (P< 0.05) fewer IgG-, IgA-, IgG1-, IgG2-, and IgG4-producing plasma cells in the connective tissue adjacent to the pocket epithelium. The reduced numbers of such patents with quiescent periodontal disease support the contention that high counts of plasma cells are indicative of more severe disease.

Adult↗

PubMed1997

Exon 6 is essential for invariant chain trimerization and induction of large endosomal structures.

Invariant chain (Ii) is a transmembrane type II protein that forms a complex with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum (ER). The membrane proximal luminal region of Ii is responsible for the non-covalent association with MHC class II molecules. Chemical cross-linking in COS cells was used to study the effect of luminal and cytoplasmic deletions on trimerization of Ii. We demonstrate that trimerization of Ii is independent of the cytosolic tail of Ii, whereas residues 162-191 (the sequence encoded by exon 6) in the luminal part of Ii are essential for trimer formation. Immunofluorescence studies of the transfected luminal deletion constructs show that the amino acids encoded by exon 6 of Ii are also essential for the induction of large endosomal vesicles. The data suggest that Ii must be in a trimeric form to modify the endosomal pathway.

Amino Acid Sequence↗

PubMed1997

Reduced serum IgG reactivities with bacteria from dental plaque in HIV-infected persons with periodontitis.

Serum samples were obtained from 44 HIV-seropositive (HIV+) and 37 HIV-seronegative (HIV-) persons that were grouped according to periodontal status. Serum IgG and IgA reactivities towards Streptococcus mutans, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis. Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum were measured by means of ELISA. HIV+ persons with chronic marginal periodontitis showed significantly lower IgG reactivities to the periodontal pathogens A. actinomycetemcomitans, P. gingivalis, P. intermedia and F. nucleatum as compared with their HIV- counterparts (p < 0.05). Specific serum IgA reactivities were similar in the two periodontitis groups, except for P. nigrescens where the HIV+ group with chronic marginal periodontitis had lower values than their systemically healthy counterparts (p < 0.05). The results indicate that HIV infection affects the humoral serum immune responses against bacteria in dental plaque; the depressed antibody responses may contribute to the increased susceptibility for periodontal infections in HIV-infected patients.

Adult↗

PubMed1997

Salivary IgA responses to bacteria in dental plaque as related to periodontal and HIV infection status.

Levels of total IgA and specific IgA reactive with Streptococcus mutans, Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum were measured by ELISA in parotid saliva from HIV+ and HIV- persons with healthy gingiva (HG), chronic gingivitis, chronic marginal periodontitis (CMP), or necrotizing ulcerative periodontitis (NUP). When the HIV+ group was compared with the HIV- group regardless of periodontal status, total salivary IgA concentration was higher in HIV+ patients, but no such difference was observed for total IgA output. HIV+ CMP displayed higher total IgA concentration as compared with HIV- CMP. No significant differences in specific IgA outputs and ratios were detected between HIV+ and HIV- subgroups with similar periodontal status. HIV+ NUP displayed increased specific IgA output towards S. mutans and increased specific IgA ratio values towards S. mutans, P. gingivalis and P. nigrescens as compared with HIV+ CMP, and increased specific IgA ratio values towards S. mutans and P. nigrescens as compared with HIV+ HG. No such differences were observed between the HIV- subgroups. In sum, salivary IgA responses to bacteria in dental plaque seem not to be related to chronic periodontal disease and HIV infection, but are possibly influenced by acute periodontal infection.

Adult↗

PubMed1995

Deletion of a C-terminal sequence of the class II-associated invariant chain abrogates invariant chains oligomer formation and class II antigen presentation.

The MHC class II-associated invariant chain (Ii) is involved in Ag processing and presentation. Physical association of MHC class II molecules with Ii and an effect of Ii on peptide loading to class II have been demonstrated, but to date these functions have not been related to a particular region of Ii. We investigated luminal deletion mutants of Ii and their role in Ag processing and presentation. IAk-expressing L cells were transfected with deletion mutants of the Ii gene and assayed for their ability to present hen egg lysozyme to three different T cell hybridomas. It is shown that the sequence aa 131-191 of Ii is important for the presentation of native hen egg lysozyme. In addition, this C terminal region is shown to be responsible for Ii oligomer formation. It is therefore conceivable that oligomer formation of Ii is a prerequisite for class II-restricted Ag processing and presentation.

Animals↗

PubMed1995

High numbers of T cells in gingiva from patients with human immunodeficiency virus (HIV) infection.

A quantitative, immunohistologic evaluation of CD3+, CD4+ and CD8+ cells was carried out on gingival biopsies from 25 HIV-infected persons with gingivitis or periodontitis and 13 HIV-seronegative persons with periodontitis. CD3+ T cells were found in all biopsies. CD8+ cells were significantly more numerous and the CD4+/CD8+ ratio was significantly decreased in the gingival connective tissue of the HIV+ patients (p < 0.05). The number of CD4+ lymphocytes subjacent to the pocket epithelium was moderately lower in the HIV+ patients as compared to the HIV patients (p < 0.05). HIV+ patients with a history of necrotizing periodontal disease had fewer CD4+ cells subjacent to the oral gingival epithelium than patients without such disease (p < 0.05). The general HIV-related changes in T lymphocyte numbers were therefore reflected in inflamed gingival tissues. HIV+ patients had, however, significantly higher CD4+/CD8+ ratios in gingiva than in peripheral blood (p < 0.05), indicating that CD4+ T cells are actively recruited to gingiva, even in cases of extreme CD4+ T lymphocytopenia.

Adult↗

PubMed1994

Serotonin-induced contraction in canine coronary artery and saphenous vein: role of a 5-HT1D-like receptor.

The identity of the serotonin (5-HT) receptor(s) that mediate(s) contraction in canine coronary artery and saphenous vein remains controversial. Ring segments of endothelium-denuded coronary artery and helical strips of saphenous vein were suspended in organ chambers for measurement of isometric force. 5-HT, alpha Me-5-HT and sumatriptan contracted both coronary artery and saphenous vein and the non-selective 5-HT receptor antagonist 1-naphthylpiperazine (100nM) blocked 5-HT- and sumatriptan-induced contraction in both tissues. The agonist rank order potency for contraction (5-HT > sumatriptan > alpha Me5-HT > 5-MeOT > 5-MeT) was similar in both tissues and was consistent with that for a 5-HT1D receptor. Oligonucleotide primers specific for the 5-HT1D receptor sequence were designed for use in a polymerase chain reaction (PCR). cDNA derived from total RNA or mRNA from canine tissues was used in the PCR. PCR resulted in the amplification of a 632 base pair sequence in both canine coronary artery and saphenous vein; consistent with that expected for the 5-HT1D receptor. Southern blot analysis, with an oligonucleotide probe internal to the sequence amplified by the PCR primers, confirmed that the sequence amplified by PCR was the 5-HT1D receptor. Thus, the 5-HT1D receptor is expressed in canine coronary artery and saphenous vein and taken together with the pharmacological data, supports the possibility that a 5-HT1D-like receptor mediates contraction in these two tissues.

5-Methoxytryptamine↗

PubMed1994

Relationship between 5-HT2A receptor mRNA density and contractility in trachea and aorta from guinea pig and rat.

The present studies document marked differences in contractile responsiveness to serotonin in trachea and aorta between guinea pig and rat. For example, the guinea pig trachea and rat aorta markedly contract in response to serotonin via activation of 5-HT2A receptors. In contrast, the rat trachea and guinea pig aorta only modestly contract to serotonin. The availability of 5-HT2A receptor selective cDNA clones from brain of both guinea pig and rat permitted molecular probes to be designed and PCR amplification studies initiated to identify and quantify 5-HT2A receptor specific mRNA in these tissues. For trachea, 3-fold higher concentrations of 5-HT2A receptor specific mRNA were found in guinea pig relative to rat trachea. These data are consistent with the more profound contractile response to serotonin in guinea pig versus rat trachea and suggest that differences in tracheal contractility to serotonin correlate with the density of 5-HT2A receptor mRNA. In contrast, although rat aorta contracted more dramatically to serotonin than guinea pig aorta, rat aorta possessed a similar concentration of 5-HT2A receptor specific mRNA as compared to guinea pig aorta. Thus, for the aorta, differences in the concentration of 5-HT2A receptor mRNA are not sufficient to explain the observed differences in contractility between tissues from guinea pig and rat. These studies documenting 5-HT2A receptor mRNA in rat trachea and guinea pig aorta, two tissues that do not markedly contract in response to serotonin indicate that 5-HT2A receptor mRNA although present, has not resulted in a receptor capable of mediating a contractile response in these tissues.

Animals↗

PubMed1994

Heat shock response in Actinobacillus actinomycetemcomitans.

The heat shock response in Actinobacillus actinomycetemcomitans, a capnophilic Gram-negative bacterial species that is implicated in the development of certain forms of periodontitis, was characterized. Different strains of A. actinomycetemcomitans were grown at 37, 42 and 48 degrees C in the presence of 35S-methionine. The bacterial cells were lysed, run on SDS-PAGE and subsequently blotted on nitrocellulose paper. After autoradiography of the blots, several protein bands from the cultures at 42 degrees C showed an increased intensity; major bands were observed at 90, 70, and 60 kDa, but increased protein synthesis was also detected at 54, 28 and 17 kDa. Nitrocellulose blots were also incubated with a panel of monoclonal and polyclonal antibodies directed to epitopes on different heat shock proteins. Strong reactivity was found with several antibodies at the position corresponding to a molecular mass of 60 kDa. The protein is probably the GroEL homologue in A. actinomycetemcomitans, a member of the 'common bacterial antigen' family.

Aggregatibacter actinomycetemcomitans↗

PubMed1994

Candidal infection of the gingiva in HIV-infected persons.

Gingival biopsies were taken from 27 HIV (human immunodeficiency virus)-seropositive persons with gingivitis or periodontitis and 16 HIV-seronegative persons with periodontitis. Sections were stained with hematoxylin and eosin or periodic acid-Schiff. Candidal hyphae and pseudohyphae were found in the parakeratinized oral epithelium in 7 specimens from the HIV-infected patient group such specimen. No fungal invasion was found in any of the biopsies from the HIV-seronegative persons. Candidal invasion was significantly more frequent (P < 0.05) in patients with a confirmed history of necrotizing periodontal diseases (5/9) than in patients without known episodes of such diseases (3/18). The most prominent histopathologic changes observed in connection with candidal invasion comprised polymorphonuclear leucocyte infiltration of the oral gingival epithelium and numerous mitoses, some of which were located suprabasally. It is suggested that Candida albicans may contribute to the development of necrotizing periodontal diseases in HIV-infected persons.

AIDS-Related Opportunistic Infections↗

PubMed1993

The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides.

Major histocompatibility complex class II molecules present peptides from an extracellular source of antigens to CD4+ T lymphocytes. The class II-associated invariant chain affects this role of alpha and beta polypeptides by restriction of peptide loading to endocytic vesicles. Up to now no specific portion of the invariant chain has been defined as the class II binding site. We constructed recombinant invariant chain genes and inspected association of the mutant invariant chains with class II polypeptides. Here we demonstrate that an extracytoplasmic sequence of the invariant chain (aa 81-109) that is only 23 residues away from the transmembrane region is essential for contact with class II polypeptides, whereas the remaining C-terminal part is dispensable for binding. The sequence of invariant-chain-derived peptides that were eluted from class II molecules is contained in this segment and may define the class II binding site of the invariant chain. The membrane-proximal position of this region suggests that the invariant chain and invariant-chain-derived peptides isolated from class II molecules bind to a domain distinct from the class II pocket.

Amino Acid Sequence↗

PubMed1993

Levels of salivary IgA antibodies reactive with bacteria from dental plaque are associated with susceptibility to experimental gingivitis.

Serum IgG, IgA and IgM and salivary IgA antibody levels reactive with extracts from Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eubacterium saburreum and Streptococcus mutans, were measured by enzyme-linked immunosorbent assay in samples from 12 persons before, during and after experimental gingivitis. The participants refrained from cleaning their teeth until 50% of their gingival units showed bleeding after gentle probing, but not longer than 15 days. Samples were taken from serum and saliva, before and during the period of experimental gingivitis, and up to 8 weeks after the start of the experiment. A pattern with minor fluctuations in specific serum and salivary antibody activities was consistently found in all patients. This indicates that immunoregulatory mechanisms succeed in maintaining unchanged antibody levels when plaque load increases. A subgroup of participants with low mean numbers of bleeding gingival units after plaque accumulation, showed significantly higher salivary IgA antibody levels reactive with S. mutans, A. actinomycetemcomitans and E. saburreum, as compared with the subgroup reaching high bleeding after probing scores (p < 0.05). When 1 person with outlying values (p < 0.05) for P. gingivalis was excluded from the tests, the former group also showed statistically significant higher salivary antibody levels to this bacterial species. High levels of salivary IgA directed against bacteria in dental plaque might thus protect against the development of gingivitis.

Adult↗

PubMed1992

Sumatriptan and 5-benzyloxytryptamine: contractility of two 5-HT1D receptor ligands in canine saphenous veins.

Sumatriptan and 5-benzyloxytryptamine are ligands with high affinity for 5-HT1D receptors in the caudate nucleus. Both compounds contracted canine saphenous veins, in vitro. Benzyloxytryptamine was less potent as a contractile agonist than sumatriptan which was less potent than serotonin. In high concentrations (greater than 10(-5) M) serotonin-induced contraction resulted, in part, from activation of alpha-adrenoceptors as determined by blockade of contraction with prazosin (10(-6) M) and idazoxan (10(-6) M). Likewise, benzyloxytryptamine but not sumatriptan also activated contractile alpha-receptors in the canine saphenous vein. Furthermore, benzyloxytryptamine antagonized contraction to sumatriptan in an apparently non-competitive fashion. Thus, benzyloxytryptamine, although possessing some alpha-receptor agonist activity, like sumatriptan, can interact with serotonin receptors in canine saphenous veins. Although effects of sumatriptan and benzyloxytryptamine quantitatively differed in canine saphenous veins, both agents showed similar affinity and agonist efficacy at 5-HT1D receptors in brain. These studies may reflect potential differences between the 5-HT1D receptor in brain and the 5-HT1-like receptor in canine saphenous veins.

Animals↗