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Y Murayama

Publications and source records attributed to Y Murayama.

At least 73 records · Page 4Linked to original sources
PubMed2000

Multiple domains interacting with Gs in the porcine calcitonin receptor.

The molecular basis for Gs activation by the calcitonin (CT) receptor was investigated. Based upon the analysis of conserved regions in G protein-coupled receptors, two nonoverlapping regions in the heptahelical porcine CT receptor (CTR) were selected as candidate Gs-interacting domains: the third intracellular loop residues 327-344 (KLKESQEAESHMYLKAVR, P3 region) and the C-tail residues 404-418 (KRQWNQYQAQRWAGR, P4 region). To assess their Gs-interacting function, we expressed these sequences in hybrid insulin-like growth factor II receptors in which the receptor native Gi-interacting domain was converted to CTR sequences. In COS cells transfected with either P3- or P4-substituted hybrid receptor, membrane adenylyl cyclase activity significantly increased. The up-regulated activity of cAMP was confirmed by measuring the transcriptional activity of the cAMP response element in cells expressing either hybrid receptor. A mutant CTR lacking the P4 region maintained positive cAMP response but with an attenuated maximal capacity to produce cAMP. In contrast, we could not assess the function of the P3 region using a conventional deletion method, as CT bound poorly to cells transfected with either of the two P3-deficient CTRs (one lacking the P3 region and the other lacking P3 but having the P3 sequence in reverse orientation). These data suggest that the third intracellular loop and the C-tail in CTR have domain-specific roles in Gs activation and that the hybrid receptor approach used here, combined with a conventional mutagenesis approach, is useful for intact cell analysis and functional dissection of G protein-coupled receptors.

Adenylyl Cyclases↗
PubMed2000

Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and cathepsin L, but not cathepsin B in cultured gingival fibroblasts.

BACKGROUND: Fibroblasts are known not only to synthesize and secrete extracellular matrix proteins, but also to degrade them for connective tissue remodeling. Drug-induced gingival overgrowth is characterized by a massive accumulation of extracellular matrix components in gingival connective tissues. Although some previous reports suggested that causative drugs stimulated the fibroblast proliferation, the results are not conclusive yet. In this study, we hypothesized that drug-induced gingival overgrowth could be a consequence of impaired ability of matrix degradation rather than an enhanced proliferation of gingival fibroblasts induced by these drugs. METHODS: Normal human gingival fibroblasts were cultured with or without either 20 microg/ml of phenytoin or 200 ng/ml of cyclosporin A. Total RNA and cellular proteins were collected every day for RT-PCR analyses and for measuring lysosomal enzyme activity. In addition, an immunohistochemical study was performed to detect lysosomal enzymes in cells from enlarged gingiva of the patients with phenytoin-induced gingival overgrowth. RESULTS: RT-PCR analyses revealed that these drugs suppressed the expression of MMP-1, TIMP-1, and cathepsin L, but not that of cathepsin B in a time-dependent manner. Then, we measured the activity of lysosomal enzymes and cathepsin B and L. The results indicated that although cathepsin B activity was not observed to be impaired, regardless of the drugs used in these cells, both total and active forms of combined activity of cathepsins B and L were suppressed in a time-dependent manner. CONCLUSIONS: The results indicate that, besides suggested effects of these drugs on gingival fibroblasts and/or on accumulated cells in the gingival tissues, extracellular matrix-degrading ability, particularly that by cathepsin L, is also suppressed by cyclosporin A and phenytoin in gingival fibroblasts, and that lysosomal enzyme plays an important role in the pathogenesis of drug-induced gingival hyperplasia.

Anticonvulsants↗
PubMed2000

Mast cells are not involved in the development of cyclosporin A-induced gingival hyperplasia: a study with mast cell-deficient mice.

BACKGROUND: A previous study suggested that mast cells (MC) are involved in the development of cyclosporin A-induced gingival hyperplasia, since an increased number of MC were observed in the tissue sections of enlarged gingiva. To determine the role of MC in gingival hyperplasia, an MC-deficient mouse model was used in the current study. METHODS: MC-deficient mice (WBB6F1xW/Wv) and their littermates (+/+) were fed sucrose-containing diets supplemented with or without varying concentrations (300, 400, 500, 600 mg) of cyclosporin A/kg of diet. After 30 days, the mice were sacrificed and the degree of gingival hyperplasia was evaluated by the appearance of the gingiva. Tissue MC were stained with toluidine blue to confirm the presence or absence of MC in the enlarged gingiva. RESULTS: Both W/Wv and +/+ mice, when fed with 600 mg cyclosporin A/kg diet for 30 days, exhibited a similar degree of gingival hyperplasia, while other test mice or control mice did not. Toluidine blue staining of the tissue sections confirmed the presence of MC in the enlarged gingiva of the +/+ mice, but not the W/Wv mice. CONCLUSIONS: These results indicate that mast cells are not necessary in the development of cyclosporin A-induced gingival hyperplasia, and that the increased number of MC observed in the enlarged gingiva may be a secondary effect of gingival hyperplasia. We also conclude that a study of mice lacking certain molecules or cells would be quite useful in determining the molecules or cell types responsible for the pathogenesis of drug-induced gingival hyperplasia.

Animals↗
PubMed2000

Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system.

OBJECT: The long-term durability of Guglielmi detachable coil (GDC) embolization of cerebral aneurysms is still unknown. The purpose of this study was to evaluate the anatomical evolution of neck remnants in aneurysms treated with GDCs. METHODS: Of 455 aneurysms treated with GDCs from 1990 to 1998 at the University of California at Los Angeles Medical Center, 178 aneurysms (39%) had residual necks postembolization. Long-term follow-up angiograms were obtained in 73 of these aneurysms in 71 patients. The mean duration of angiographic follow up was 17.3 months. Twenty-four of the aneurysms were small with small necks, 24 were small with wide necks, 15 were large, and 10 were giant aneurysms. In small aneurysms with small necks, postembolization angiography revealed 12 aneurysms (50%) with progressive thrombosis, eight (33%) unchanged, and four (17%) with recanalization. In small aneurysms with wide necks, six (25%) had progressive thrombosis, eight (33%) remained unchanged, and 10 (42%) had recanalization. In large aneurysms, two (13%) were unchanged and 13 (87%) had recanalization. Of the giant aneurysms only one (10%) remained unchanged and nine (90%) had recanalization. Overall, 18 aneurysms (25%) exhibited progressive thrombosis, 19 (26%) remained unchanged, and 36 (49%) displayed recanalization on follow-up angiography. During the last 2 years of the study, the recanalization rate decreased and a higher rate of progressive thrombosis was noted in aneurysms with small necks. These positive changes are related to important new technical developments. CONCLUSIONS: Treatment with GDCs appears to be effective and the results permanent in most small aneurysms with small necks. However, there are important technical limitations in the current GDC technology that prevent recanalization in wide-necked or large or giant aneurysms.

Adult↗
PubMed2000

Endovascular treatment of experimental aneurysms by use of a combination of liquid embolic agents and protective devices.

BACKGROUND AND PURPOSE: The use of liquid embolic agents for embolization of cerebral aneurysms has been reported in the neurosurgical literature. The most important limitation of this technique is the relatively poor control of migration of the liquid embolic agent into the parent artery. We performed an experimental aneurysm study using a liquid embolic agent and different protective devices to evaluate the safety and technical feasibility of this endovascular technique. METHODS: Forty lateral aneurysms were surgically constructed on 20 common carotid arteries of swine. Onyx alone was used to obliterate eight aneurysms. Onyx was also used in combination with microcoils (n = 11), microstents (n = 6), balloons inflated proximally to the neck of the aneurysm (n = 6), and across the neck of the aneurysm (n = 7). One control aneurysm was embolized with Guglielmi detachable coils (GDCs) alone. RESULTS: The use of a microballoon across the neck of the aneurysm, a microstent deployed across the neck of the aneurysm, or the deposit of GDCs into the aneurysm allowed faster and more complete filling of the aneurysm with Onyx. However, these protection devices did not totally preclude intractable migration of Onyx into the parent artery (migration rate, 9-33%). CONCLUSION: Although complete occlusion of experimental aneurysms with Onyx is feasible using protective devices, migration of the liquid embolic agent into the parent artery or intracranially remains a difficult challenge. Further experimental studies need to be performed to master this technique and to select those aneurysms that can be safely treated in clinical practice.

Animals↗
PubMed2000

Endovascular treatment of basilar tip aneurysms using Guglielmi detachable coils: anatomic and clinical outcomes in 73 patients from a single institution.

OBJECTIVE: Seventy-three consecutive patients with 75 basilar tip aneurysms were treated with Guglielmi detachable coil (GDC) technology. Their anatomic and clinical outcomes are discussed. METHODS: Seventy-five basilar tip aneurysms were treated with the GDC system at the University of California, Los Angeles Medical Center from 1990 to 1999. The average age of the population was 48.3 years (range, 28-82 yr). Forty-two patients (57.5%) presented with acute subarachnoid hemorrhage, 8 patients (10.9%) had unruptured aneurysms with mass effect, and 23 patients (31.5%) had incidental aneurysms. Thirty-one aneurysms (41.3%) were small with a small neck, 18 (24%) were small with a wide neck, 16 (21.3%) were large, and 10 (13.3%) were giant aneurysms. RESULTS: Immediate anatomic outcomes demonstrated complete or near-complete occlusion in 64 aneurysms (85.3%) and incomplete occlusion in 7 aneurysms (9.3%). Four aneurysms (5.3%) could not be embolized because of anatomic difficulties. Of the 69 patients treated with GDCs, 63 patients (91.3%) remained neurologically intact or unchanged from their initial clinical status. Procedure-related morbidity and mortality were 4.1% and 1.4%, respectively. Long-term follow-up angiograms were obtained in 41 patients with 42 aneurysms. Thirty aneurysms (71.4%) demonstrated complete or near-complete occlusion. One incompletely embolized giant aneurysm ruptured during the follow-up period. CONCLUSION: In contrast to surgical clipping of basilar tip aneurysms, the main technical challenge of the Guglielmi detachable coiling procedure depends on the shape of the aneurysm, not its location. The results of this study indicate that endovascular GDC technology is an appropriate therapeutic alternative in ruptured or unruptured basilar tip aneurysms regardless of patient age, clinical presentation, clinical status, or timing of treatment.

Adult↗
PubMed2000

Negative effects of chronic inflammatory periodontal disease on diabetes mellitus.

Periodontal disease is the result of a complex interplay of bacterial infection and host responses, and is often modified by various systemic diseases such as diabetes mellitus. Such diseases are capable of affecting the periodontium and/or the treatment of periodontal disease. However, recent research has changed our concept of how periodontal disease should be treated. Here we present several concerns directed towards the periodontal therapy of patients with diabetes mellitus based on our studies. When treating periodontitis patients who have diabetes mellitus it is important to consider the type of diabetes. Patients with non-insulin dependent diabetes mellitus can be further classified according to the degree of insulin resistance, since recent epidemiological studies have suggested that successful anti-microbial therapy might result in improved insulin resistance in highly insulin resistant patients. Because the major contributing factor for insulin resistance is currently considered to be the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), and because periodontal surgery may cause transient bacteremia which may up-regulate the serum TNF-alpha level, which in turn suppresses insulin action, patients should be strictly treated non-surgically and their serum TNF-alpha levels should be periodically monitored. On the other hand, diabetic patients positive for serum anti-glutamate decarboxylase auto-antibody should be examined for the source of this antibody, since 1) gingival and periodontal ligament fibroblasts were found to express glutamate decarboxylase, and 2) some otherwise healthy periodontitis patients develop anti-glutamate decarboxylase antibody. Thus, chronic periodontitis may influence the level of this antibody which is widely used as a predictive marker for slowly progressive insulin dependent diabetes mellitus. Not only is periodontal disease thereby affected by systemic diseases, but carefully managed periodontal therapy may also have a positive effect on the general health of patients with systemic diseases.

Anti-Bacterial Agents↗
PubMed1999

The shbg Gene and Hormone Dependence of Breast Cancer: A Novel Mechanism of Hormone Dependence of MCF-7 Human Breast Cancer Cells Based upon SHBG.

BACKGROUND: SHBG (sex hormone binding globulin) is a 45 kDa glycoprotein thatbinds sex steroid with high specificity and affinity. SHBG is produced in various tissues including breast, liver, endometrium, and prostate via activated ER alpha and is secreted into plasma. SHBG regulates the activity of bioavailable sex steroid in plasma and in cells and also modulates cell growth regulation. METHODS: The predictive value of SHBG on the efficacy of hormone therapy against human breast cancer was determined. To evaluate the role of shbg gene expression in estrogen-dependent cell growth of MCF-7 breast cancer, cDNA cloning and determination of the expression of the shbg gene of MCF-7 cells was performed using PCR, RT-PCR Southern blotting. RESULTS: The SHBG titer (17 beta -estradiol binding capacity of SHBG) showed high predictability for the hormone dependence of breast cancer. Tumors of patientswith high SHBG titers showed a 91.8% response rate (N = 49). In contrast, tumors of patients with low SHBG titers showed only an 8.2% response rate (N = 61). >From our experimental results using MCF-7 cells, it is suggested that the SHBG titer includes SHBG secreted from liver and breast cancer cells. MCF-7 cells showed high expression of the wild type shbg gene, hybridized with Hammond's SHBG probe, which represents the 3'portion of SHBG-cDNA cloned from hepatocytes. E2 (17 beta-estradiol) induced the expression of the wild type shbg gene. However, the exon VII splicing variant of the shbg gene did not respond to E2 induction. CONCLUSIONS: From our results and the reports of other investigators, it is suggested that loss of hormone dependence in breast cancer may be caused by the loss of wild type shbg gene and the appearance of the exon VII splicing variant.The shbg-E2 complex binds to SHBG receptor (SHBGR) in cell membrane and internalizes through SHBGR mediated endocytosis causing the production of intracellularcAMP and E2-responsive second messenger. SHBG functions as a nuclear protein. From these data, we prepared a model of a novel mechanism of hormone dependence of breast cancer based upon SHBG and the shbg gene.

Journal Article↗
PubMed1999

T1 Breast Cancer Associated with Von Recklinghausen's Neurofibromatosis.

A rare case of breast cancer associated with von Recklinghausen s neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis. A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skinretraction in October, 1998. The patient had von Recklinghausen fs disease (neurofibromatosis type 1). The TNM clinical staging was T1cN0M0. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pT1cN1aM0. Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.

Journal Article↗
PubMed1999

Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alpha-fetoprotein gene.

BACKGROUND AND OBJECTIVES: Development of the system to express a suicide gene selectively in tumor cells is essential for gene therapy. We constructed a plasmid containing the diphtheria toxin A (DTA) fragment linked to human alpha-fetoprotein (AFP) promoter and enhancer, and tested whether it can exert its cytocidal effect selectively on AFP-producing cells. METHODS: The chloramphenical acetyltransferase (CAT) reporter gene or DTA gene was linked to the 5' upstream region of the AFP gene. The plasmids were transfected into AFP-producing or non-producing cells by the lipopolyamine-coated DNA method. Expression of CAT activity and effects on cell growth of transfected cells were assessed. RESULTS: When the AFP-producing cells HuH-7 or HepG2 were cotransfected with CAT reporter plasmid and pAF5.1DTA plasmid, the CAT activity was greatly suppressed. In contrast, cotransfection with pAF5.1DTA-R, the inversely inserted DTA gene, did not inhibit CAT activity. Furthermore, cell growth of HuH-7 cells transfected with pAF5.1DTA plasmid was significantly inhibited compared with HuH-7 cells transfected with DTA-R plasmid. CONCLUSIONS: Our results indicate that selective killing of AFP-producing cells will be attained by introducing the DTA gene linked to the promoter and enhancer region of AFP.

Carcinoma, Hepatocellular↗
PubMed1999

Transvenous Doppler guidewire sonographic monitoring during treatment of a complex vertebral arteriovenous fistula associated with neurofibromatosis type 1.

A Doppler sonographic guidewire was used to monitor incremental changes in draining vein (DV) flow during endovascular occlusion of a complex vertebral arteriovenous fistula (AVF) in a patient with neurofibromatosis type 1. Transvenous monitoring of average peak velocity (APV) and the maximum-minus-minimum peak velocity (MxPV-MnPV) demonstrated a progression from a highly pulsatile, fast flow before embolization to a nonpulsatile, slow flow indicating a successful occlusion of the AVF (hemodynamic endpoint of treatment). Prior to this, apparent angiographic occlusion of the AVF was thought to signify a successful endpoint; however, persistently elevated values for APV and MxPV-MnPV in the DV signalled the presence of an additional contralateral arterial contribution. Transvenous monitoring of flow velocity appears to be ideally suited to establishing a hemodynamic endpoint of embolotherapy in the presence of complex arteriovenous shunting, as may occur with the vasculopathy of neurofibromatosis.

Adult↗
PubMed1999

An African green monkey lacking peripheral CD4 lymphocytes that retains helper T cell activity and coexists with SIVagm.

Natural infection with simian immunodeficiency virus (SIV) is known to occur in the African green monkey (AGM). The actual onset of the disease has not been recognized in SIVagm infected AGM, and the precise reason for such apathogenicity in the AGM remains unclear. We reported previously that AGM peripheral CD4 lymphocytes underwent a peculiar differentiation from CD4+ to CD4- cells after in vitro activation, and we inferred that the AGM does not fall into a fatal immunodeficient state because of the generation of CD4- helper T cells in vivo. To evaluate this possibility, we examined the relationship between CD4 expression and helper T cell activity in the naturally infected AGM. We identified a healthy monkey almost lacking CD4 T cells in the periphery. This AGM showed no signs and symptoms of immunodeficiency and retained a helper T cell activity in antibody production comparable to those of CD4+ AGMs. In addition, SIVagm could be isolated from CD8+ lymphocytes in the CD4- AGM. These observations suggest that a unique host-virus adaptation has developed in the AGM, and may be helpful in explaining the fundamental reason for the apathogenicity occurring in this monkey.

Amino Acid Sequence↗
PubMed1999

U5 monoclonal antibody identifies a novel lymphocyte surface antigen preferentially expressed in human circulating natural killer cells with high cytotoxic activity.

U5 monoclonal antibody (mAb), developed against Japanese monkey lymphocytes, identified a glycoprotein of 32 000 MW that is expressed in a subset of human circulating natural killer (NK) cells. The distribution of U5 molecules was restricted among CD16+ cells, and U5 antigen was preferentially expressed in the CD38+ subset. U5+ CD16+ CD56+ cells were highly active on NK assay against K562 target cells. Variations in cytolytic activities and mRNA expression of perforin, granzyme B and Fas ligand (FasL) were observed in U5- CD16+ CD56+ cells depending on the donor. We found that in some donors, a phenotypically mature (CD16+ CD56+) but functionally immature subset was present in the peripheral circulation. The U5- CD16+ CD56+ cells of some donors exhibited negligible cytolytic activity with no detectable expression of the above mRNAs, whereas those of the other donors had a significant but lower cytolytic activity with a reduced expression of granzyme B mRNA as compared with those of U5+ CD16+ CD56+ cells. Concanavalin A (Con A) stimulation induced an expression of U5 antigen in U5- CD16+ CD56+ cells accompanied by an up-regulation of granzyme B mRNA expression. These findings suggest that U5 antigen may be a novel molecule involved in the maturation or differentiation of human circulating NK cells.

Adult↗
PubMed1999

Balloon-assisted Guglielmi detachable coiling of wide-necked aneurysms: Part I--experimental evaluation.

OBJECTIVE: Balloon-assisted technique is a promising technical adjunct to use of Guglielmi detachable coils for embolization of wide-necked aneurysms. In this study using experimental aneurysms in swine, the safety and long-term efficacy of this technique were evaluated. METHODS: Sixteen wide-necked aneurysms (sidewall model) were surgically created in common carotid arteries of swine. In the acute study of eight aneurysms, intra-aneurysmal pressure changes were recorded during balloon inflation in different positions of the balloon relative to the neck of the aneurysm. In the chronic study, eight aneurysms were treated with this technique, and follow-up angiography was performed 14 days postembolization. The animals were then killed for macroscopic evaluation. RESULTS: In the acute study, the systolic intra-aneurysmal blood pressure increased with balloon inflation at the distal portion of the neck and with balloon inflation/occlusion across the entire neck of the aneurysm. In the chronic study, seven of eight cases were embolized with satisfactory occlusion, and six showed no coil displacement on the follow-up angiogram. In five cases, macroscopic evaluation of the aneurysm showed that the coils were compacted at the neck of the aneurysm with a concave shape consistent with the shape of the inflated balloon across its neck. CONCLUSION: This preliminary study indicates that balloon-assisted Guglielmi detachable coiling technology may produce a temporary increase of pressure within the aneurysm while occluding the aneurysmal neck during coil delivery. This sudden change of intra-aneurysmal pressure may potentially be the cause-of aneurysm rupture in the clinical setting. The balloon must be inflated and deflated very slowly to minimize these potentially risky hemodynamic changes. Although angiographic follow-up showed successful obliteration of aneurysms, further long-term angiographic studies are necessary to establish the durability of this technique.

Animals↗
PubMed1999

Ballonn-assisted Guglielmi detachable coiling of wide-necked aneurysma: Part II--clinical results.

OBJECTIVE: To demonstrate the indications and efficacy of balloon-assisted Guglielmi detachable coiling (BAGDC). METHODS: BAGDC was used for 23 patients (19 women and 4 men; mean age, 55 yr) (17%) of a series of 136 consecutive patients who underwent Guglielmi detachable coiling of aneurysms. Every aneurysm had a wide neck, and 57% were large (11-25 mm in diameter). In each case, a nondetachable silicone balloon was advanced in the parent artery and inflated to occlude the neck of the aneurysm and stabilize the Guglielmi detachable coil delivery microcatheter at the aneurysm neck. Guglielmi detachable coils were then deposited. The balloon was then deflated to verify appropriate coil placement and stability, and finally, the Guglielmi detachable coils were detached. This process was repeated until the aneurysm was suitably embolized. RESULTS: One hundred percent aneurysm embolization was achieved in 19 patients (83%), and 95 to 100% embolization was achieved in 4 patients (17%). Twenty-two patients (96%) were at their preprocedure neurological baseline after the procedure. There were three complications in the study. One patient died after sustaining subarachnoid hemorrhage-induced vasospasm followed by a hemorrhagic infarction. She had undergone an unsuccessful clip ligation of her aneurysm. A second patient developed an intra-arterial thrombus at the site of balloon deployment. She sustained ischemic events that were treated with thrombolysis and anticoagulation. She made a complete recovery. A third patient developed an intra-arterial thrombus that was noted during the procedure. She was treated with intra-arterial thrombolysis and experienced no clinical sequelae. No permanent complications could be attributed to the BAGDC technique. The median clinical follow-up time was 10 months. No patient required additional treatment or developed a recurrent aneurysm neck or lumen. CONCLUSION: BAGDC is a promising adjunct to the treatment of wide-necked aneurysms. The balloon serves two purposes: it stabilizes the microcatheter in the aneurysm during coil delivery, and it forces the coil to assume the three-dimensional shape of the aneurysm without impinging on the parent artery.

Adult↗
PubMed1999

Role of soluble interleukin-6 receptor in inflamed gingiva for binding of interleukin-6 to gingival fibroblasts.

Interleukin-6 (IL-6), frequently detected in periodontitis, is known to mediate important signals in the inflammatory cytokine network. Gingival fibroblasts (GF) secrete cytokines upon stimulation with inflammatory mediators. However, it is not clear if GF respond to IL-6. We examined the IL-6 receptor gene expression in GF. Furthermore, we tested whether GF are target cells for IL-6 by examination of binding of IL-6. GF were found to contain trace amounts of mRNA for IL-6 receptor (IL-6R), but had high levels of mRNA for 130-kDa glycoprotein (gp130), which is a signal transducer for IL-6/IL-6R complex. Based on this observation, we hypothesized that IL-6 could bind GF if exogenous soluble forms of IL-6R (sIL-6R) existed in the gingiva or culture condition. Thus, we investigated the existence of sIL-6R in gingiva using enzyme-linked immunosorbent assay and whether sIL-6R influenced the binding of IL-6 to GF in vitro. In inflamed gingiva, sIL-6R was detected and its concentration ranged from 150 to 700 pg/microgram protein. The sIL-6R enhanced the binding of IL-6 to GF in a dose-dependent manner. This enhancement was inhibited by an antibody against gp130, suggesting that the IL-6/sIL-6R complex bound to the fibroblasts via gp130. These data demonstrated that gingival fibroblasts can be target cells for IL-6 in the presence of appropriate amounts of sIL-6R. This situation may exist during inflammation in periodontal tissue.

Adult↗
PubMed1999

HLA genetics for diagnosis of susceptibility to early-onset periodontitis.

Human leukocyte antigens (HLA) are essential in the recognition of foreign antigens in humoral immune response, which is genetically predetermined. Susceptibility to certain diseases that involve the immune response has been studied in relation to distinct HLA types. Although some diseases have been found to correlate to specific HLA loci positively, it has been difficult to isolate HLA types that predispose patients to periodontal destruction. Here, we review the current knowledge and recent advances in HLA genetics and its biology, which determine susceptibility to early-onset periodontitis (EOP). The HLA-DRB1*1501-DQB1*0602 genotype has been found with increasing frequency in EOP patients. This HLA genotype expresses aspartic acid at position 57 and glycine at position 70 on the DQ beta chain, suggesting a capability to bind certain bacterial antigens. The T cell response against the outer membrane protein (Ag53) of Porphyromonas gingivalis was examined via this HLA genotype. Strong T cell response against Ag53 p141-161 was inhibited partially by anti-DR antibody, but not by anti-DQ antibody. Possible host and bacterial peptides capable of binding DRB1*1501 were elucidated when the peptide sequence was compared to gene and protein databases. These results suggest that patients who have the HLA-DRB1*1501-DQB1*0602 genotype may have an accelerated T cell response to certain periodontopathic bacteria such as P. gingivalis in hyperimmune reactions and thus increased susceptibility to EOP.

Aggressive Periodontitis↗